Summary: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).

Top Publications

  1. ncbi Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
    D R Matthews
    Diabetologia 28:412-9. 1985
  2. pmc Mechanisms for insulin resistance: common threads and missing links
    Varman T Samuel
    Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 148:852-71. 2012
  3. ncbi Insulin signalling and the regulation of glucose and lipid metabolism
    A R Saltiel
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Nature 414:799-806. 2001
  4. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
  5. pmc A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
    Christopher B Newgard
    Sarah W Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA
    Cell Metab 9:311-26. 2009
  6. doi The genetics of ageing
    Cynthia J Kenyon
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 464:504-12. 2010
  7. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
  8. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
  9. pmc Insulin sensitivity: modulation by nutrients and inflammation
    Simon Schenk
    Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093, USA
    J Clin Invest 118:2992-3002. 2008
  10. ncbi Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients
    K Hotta
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
    Arterioscler Thromb Vasc Biol 20:1595-9. 2000

Research Grants

Detail Information

Publications483 found, 100 shown here

  1. ncbi Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
    D R Matthews
    Diabetologia 28:412-9. 1985
    The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop...
  2. pmc Mechanisms for insulin resistance: common threads and missing links
    Varman T Samuel
    Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 148:852-71. 2012
    b>Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway...
  3. ncbi Insulin signalling and the regulation of glucose and lipid metabolism
    A R Saltiel
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Nature 414:799-806. 2001
    ..In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, ..
  4. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
    ..We demonstrated that overexpression of PTEN, a putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in human 293 cells without effecting insulin-induced phosphoinositide 3-kinase ..
  5. pmc A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
    Christopher B Newgard
    Sarah W Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA
    Cell Metab 9:311-26. 2009
    ..acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance...
  6. doi The genetics of ageing
    Cynthia J Kenyon
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 464:504-12. 2010
    ..Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions...
  7. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
    Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year.
  8. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
    ..daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member...
  9. pmc Insulin sensitivity: modulation by nutrients and inflammation
    Simon Schenk
    Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093, USA
    J Clin Invest 118:2992-3002. 2008
    b>Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes...
  10. ncbi Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients
    K Hotta
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
    Arterioscler Thromb Vasc Biol 20:1595-9. 2000
    ..Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels...
  11. ncbi Mitochondrial dysfunction and type 2 diabetes
    Bradford B Lowell
    Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
    Science 307:384-7. 2005
    Maintenance of normal blood glucose levels depends on a complex interplay between the insulin responsiveness of skeletal muscle and liver and glucose-stimulated insulin secretion by pancreatic beta cells...
  12. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002 Akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. TSC2 is inactivated by Akt-dependent phosphorylation, which destabilizes TSC2 and disrupts its interaction with ..
  13. doi In vivo reprogramming of adult pancreatic exocrine cells to beta-cells
    Qiao Zhou
    Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nature 455:627-32. 2008
    ..essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a ..
  14. pmc Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Science 313:1137-40. 2006
    Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes...
  15. doi 10-year follow-up of intensive glucose control in type 2 diabetes
    Rury R Holman
    Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom
    N Engl J Med 359:1577-89. 2008
    ..We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes...
  16. doi The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
    C J Currie
    School of Medicine, Cardiff University, The Pharma Research Centre, Cardiff Medicentre, Cardiff, CF14 4UJ, UK
    Diabetologia 52:1766-77. 2009
    ..We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues.
  17. ncbi Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes
    Eric J Rulifson
    Department of Developmental Biology, Beckman Center B300, Stanford University, Stanford, CA 94305 5329, USA
    Science 296:1118-20. 2002
    In the fruit fly Drosophila, four insulin genes are coexpressed in small clusters of cells [insulin-producing cells (IPCs)] in the brain...
  18. ncbi Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
    Joseph T Rodgers
    Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 434:113-8. 2005
    ..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan...
  19. doi MicroRNAs 103 and 107 regulate insulin sensitivity
    Mirko Trajkovski
    Institute for Molecular Systems Biology, ETH Zurich, Wolfgang Pauli Strasse 16, CH 8093 Zurich, Switzerland
    Nature 474:649-53. 2011
    Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes...
  20. ncbi Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin
    Samantha L Bowker
    Institute of Health Economics, Edmonton, Alberta, Canada
    Diabetes Care 29:254-8. 2006
    ..We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.
  21. pmc Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals
    David Patsouris
    Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Cell Metab 8:301-9. 2008
    ..and produces high levels of proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance...
  22. pmc Lipid-induced insulin resistance: unravelling the mechanism
    Varman T Samuel
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536 8012, USA
    Lancet 375:2267-77. 2010
    b>Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points...
  23. ncbi Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
    Geert J P L Kops
    Department of Physiological Chemistry, University Medical Center Utrecht and Center for Biomedical Genetics, 3584 CG Utrecht, The Netherlands
    Nature 419:316-21. 2002
    ..The model of Forkhead involvement in regulating longevity stems from genetic analysis in Caenorhabditis elegans, and we conclude that this model also extends to mammalian systems...
  24. ncbi Nonalcoholic fatty liver disease: a feature of the metabolic syndrome
    G Marchesini
    Unit of Metabolic Diseases, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy
    Diabetes 50:1844-50. 2001
    b>Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2)...
  25. pmc Resveratrol improves health and survival of mice on a high-calorie diet
    Joseph A Baur
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 444:337-42. 2006
    ..Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) ..
  26. ncbi PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
    Vamsi K Mootha
    Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
    Nat Genet 34:267-73. 2003
    ..Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity...
  27. ncbi Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40
    Yasuaki Itoh
    Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Wadai 10, Tsukuba, Ibaraki 300 4293, Japan
    Nature 422:173-6. 2003
    Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue...
  28. pmc Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
    Ethan J Anderson
    Metabolic Institute for the Study of Diabetes and Obesity, East Carolina University, Greenville, North Carolina 27834, USA
    J Clin Invest 119:573-81. 2009
    High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease...
  29. pmc Endocrine regulation of energy metabolism by the skeleton
    Na Kyung Lee
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Cell 130:456-69. 2007
    ..and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity...
  30. ncbi Visfatin: a protein secreted by visceral fat that mimics the effects of insulin
    Atsunori Fukuhara
    Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Science 307:426-30. 2005
    ..Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice...
  31. ncbi Critical nodes in signalling pathways: insights into insulin action
    Cullen M Taniguchi
    Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    Nat Rev Mol Cell Biol 7:85-96. 2006
    ..Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role using insulin signalling as a model system.
  32. ncbi Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
    Mahvash Zakikhani
    Department of Oncology, McGill University, Montreal, Quebec, Canada
    Cancer Res 66:10269-73. 2006
    ..This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with ..
  33. pmc Obesity-associated improvements in metabolic profile through expansion of adipose tissue
    Ja Young Kim
    Department of Cell Biology, Albert Einstein College of Medicine, New York, New York, USA
    J Clin Invest 117:2621-37. 2007
    Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue...
  34. pmc The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
    Bolormaa Vandanmagsar
    Laboratory of Neuroendocrine Immunology, Louisiana State University, Baton Rouge, Louisiana, USA
    Nat Med 17:179-88. 2011
    ..with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity...
  35. doi Bariatric surgery versus conventional medical therapy for type 2 diabetes
    Geltrude Mingrone
    Department of Internal Medicine, Universita Cattolica S Cuore, Largo A Gemelli 8, 00168 Rome, Italy
    N Engl J Med 366:1577-85. 2012
    ..Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed...
  36. ncbi Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group
    R C Turner
    Radcliffe Infirmary, Oxford, England
    JAMA 281:2005-12. 1999
    Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less ..
  37. ncbi Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity
    E Bonora
    Division of Endocrinology and Metabolic Diseases, University of Verona Medical School, Italy
    Diabetes Care 23:57-63. 2000
    To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans.
  38. ncbi Regulation of aging and age-related disease by DAF-16 and heat-shock factor
    Ao Lin Hsu
    Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143 2200, USA
    Science 300:1142-5. 2003
    ..We find that HSF-1, like the transcription factor DAF-16, is required for daf-2-insulin/IGF-1 receptor mutations to extend life-span...
  39. pmc Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism
    Haiming Cao
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Cell 134:933-44. 2008
    Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism...
  40. pmc Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans
    Mikkel Christensen
    Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, Copenhagen, Denmark
    Diabetes 60:3103-9. 2011
    To evaluate the glucose dependency of glucose-dependent insulinotropic polypeptide (GIP) effects on insulin and glucagon release in 10 healthy male subjects ([means ± SEM] aged 23 ± 1 years, BMI 23 ± 1 kg/m(2), and HbA(1c) 5.5 ± 0.1%).
  41. pmc Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study
    M Peyrot
    Department of Sociology, Loyola University of Maryland, Baltimore, MD 21210 2699, USA
    Diabet Med 29:682-9. 2012
    To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens.
  42. ncbi AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
    Yasuhiko Minokoshi
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 428:569-74. 2004
    ..paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding...
  43. pmc neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas
    G Gradwohl
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université Louis Pasteur, F 67404 Illkirch, France
    Proc Natl Acad Sci U S A 97:1607-11. 2000
    ..We show herein that ngn3-positive cells coexpress neither insulin nor glucagon, suggesting that ngn3 marks early precursors of pancreatic endocrine cells...
  44. ncbi A central role for JNK in obesity and insulin resistance
    Jiro Hirosumi
    Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
    Nature 420:333-6. 2002
    Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood...
  45. pmc Obesity and metabolic syndrome in circadian Clock mutant mice
    Fred W Turek
    Department of Neurology, Northwestern University, Evanston, IL 60208, USA
    Science 308:1043-5. 2005
    ..These results suggest that the circadian clock gene network plays an important role in mammalian energy balance...
  46. ncbi Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance
    Daniela M L Tsukumo
    Department of Internal Medicine, State University of Campinas, Campinas, Sao Paulo, Brazil
    Diabetes 56:1986-98. 2007
    Obesity is associated with insulin resistance and a state of abnormal inflammatory response...
  47. pmc Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes
    Biliana Marcheva
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Nature 466:627-31. 2010
    ..During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be ..
  48. pmc Oxidative stress, insulin signaling, and diabetes
    Justin L Rains
    Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
    Free Radic Biol Med 50:567-75. 2011
    ..Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ..
  49. pmc Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial
    D Russell-Jones
    Department of Diabetes and Endocrinology, Royal Guildford Hospital, UK
    Diabetologia 52:2046-55. 2009
    The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.
  50. pmc Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure
    Chutima Talchai
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell 150:1223-34. 2012
    ..We propose that dedifferentiation trumps endocrine cell death in the natural history of β cell failure and suggest that treatment of β cell dysfunction should restore differentiation, rather than promoting β cell replication...
  51. ncbi Effect of treatment of gestational diabetes mellitus on pregnancy outcomes
    Caroline A Crowther
    Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia
    N Engl J Med 352:2477-86. 2005
    ..We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications...
  52. pmc Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes
    Adilson Guilherme
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nat Rev Mol Cell Biol 9:367-77. 2008
    Acquired resistance to the action of insulin to stimulate glucose transport in skeletal muscle is associated with obesity and promotes the development of type 2 diabetes...
  53. pmc Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss
    Fabrizio Thorel
    Department of Cell Physiology and Metabolism, University of Geneva Faculty of Medicine, 1 rue Michel Servet, CH 1211 Geneva 4, Switzerland
    Nature 464:1149-54. 2010
    Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime...
  54. pmc Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
    Richa Saxena
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 42:142-8. 2010
    ..e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1...
  55. ncbi Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
    Science 306:457-61. 2004
    ..This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation ..
  56. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
    ..mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers...
  57. pmc Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long)
    Bernard Zinman
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes Care 35:2464-71. 2012
    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).
  58. pmc Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans
    Jennifer M A Tullet
    Section on Developmental and Stem Cell Biology, Joslin Diabetes Center Department of Pathology, Harvard Medical School Harvard Stem Cell Institute, 1 Joslin Place, Boston, MA 02215, USA
    Cell 132:1025-38. 2008
    b>Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C...
  59. doi The insulin and insulin-like growth factor receptor family in neoplasia: an update
    Michael Pollak
    Lady Davis Research Institute and McGill University, Montreal, Quebec H3T1E2, Canada
    Nat Rev Cancer 12:159-69. 2012
    Although several early phase clinical trials raised enthusiasm for the use of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, initial Phase III results in unselected patients have been ..
  60. pmc Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity
    Dudley W Lamming
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 335:1638-43. 2012
    ..Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of ..
  61. ncbi A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
    D E Cummings
    University of Washington, VA Puget Sound Health Care System and Harborview Medical Center, Seattle, Washington 98108, USA
    Diabetes 50:1714-9. 2001
    ..Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 ..
  62. pmc Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes
    Ying Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    J Pathol 225:54-62. 2011
    ..Here, we investigated the brain insulin-PI3K-AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM-AD and seven ..
  63. ncbi Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
    A J Sanyal
    Division of Gastroenterology Hepatology, Department of Internal Medicine, Virginia Commonwealth University Medical College of Virginia, Richmond, Virginia 23298 0711, USA
    Gastroenterology 120:1183-92. 2001
    ..We tested the hypothesis that NASH is associated with 2 defects: (1) peripheral insulin resistance, which increases lipolysis, delivery of free fatty acids (FFA) to the liver, and hepatic fatty acid ..
  64. ncbi Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta)
    H Cho
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 292:1728-31. 2001
    Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver...
  65. ncbi AMP-activated protein kinase in metabolic control and insulin signaling
    Mhairi C Towler
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Circ Res 100:328-41. 2007
    ..Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining ..
  66. pmc Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB
    Dongsheng Cai
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA
    Nat Med 11:183-90. 2005
    ..These mice exhibit a type 2 diabetes phenotype, characterized by hyperglycemia, profound hepatic insulin resistance, and moderate systemic insulin resistance, including effects in muscle...
  67. ncbi The endocrine regulation of aging by insulin-like signals
    Marc Tatar
    Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA
    Science 299:1346-51. 2003
    Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging...
  68. ncbi Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
    Varman T Samuel
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 279:32345-53. 2004
    ..accumulation and provides a model of non-alcoholic fatty liver disease in which to study the mechanism of hepatic insulin resistance...
  69. pmc Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans
    Kimber L Stanhope
    Department of Molecular Biosciences, UCD, Davis, California 95616, USA
    J Clin Invest 119:1322-34. 2009
    Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance...
  70. ncbi Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1
    Sung Hee Um
    Department of Genome Science, Genome Research Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, Ohio 45237, USA
    Cell Metab 3:393-402. 2006
    Nutrient overload leads to obesity, insulin resistance, and often type 2 diabetes...
  71. ncbi Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
    M Elchebly
    Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada, H3G 1Y6
    Science 283:1544-8. 1999
    Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling...
  72. pmc A multicenter, randomized trial of treatment for mild gestational diabetes
    Mark B Landon
    Department of Obstetrics and Gynecology, Ohio State University, Columbus, USA
    N Engl J Med 361:1339-48. 2009
    ..It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes...
  73. ncbi A pancreatic islet-specific microRNA regulates insulin secretion
    Matthew N Poy
    Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 432:226-30. 2004
    ..Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion...
  74. pmc Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study
    Adam G Tabak
    Department of Epidemiology and Public Health, University College London, London, UK
    Lancet 373:2215-21. 2009
    ..We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes.
  75. pmc A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
    Alisa K Manning
    Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
    Nat Genet 44:659-69. 2012
    ..pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance...
  76. pmc The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43
    Ikuo Kimura
    Department of Pharmacogenomics, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo ku, Kyoto 606 8501, Japan
    Nat Commun 4:1829. 2013
    ..affects nutrient acquisition and energy regulation of the host, and can influence the development of obesity, insulin resistance, and diabetes...
  77. ncbi Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery
    David E Cummings
    Department of Medicine, University of Washington the Veterans Affairs Puget Sound Health Care System, Seattle 98108, USA
    N Engl J Med 346:1623-30. 2002
    ..Because ghrelin is produced primarily by the stomach, weight loss after gastric bypass surgery may be accompanied by impaired ghrelin secretion...
  78. ncbi International trial of the Edmonton protocol for islet transplantation
    A M James Shapiro
    Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada
    N Engl J Med 355:1318-30. 2006
    ..We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol)...
  79. doi The many faces of insulin-like peptide signalling in the brain
    Ana M Fernandez
    Cajal Institute, CSIC and CIBERNED, Avenida Doctor Arce, 37, Madrid 28002, Spain
    Nat Rev Neurosci 13:225-39. 2012
    Central and peripheral insulin-like peptides (ILPs), which include insulin, insulin-like growth factor 1 (IGF1) and IGF2, exert many effects in the brain...
  80. doi Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial
    Michaela Diamant
    Diabetes Centre, VU University Medical Centre, Amsterdam, Netherlands
    Lancet 375:2234-43. 2010
    ..We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets.
  81. pmc Breaking up prolonged sitting reduces postprandial glucose and insulin responses
    David W Dunstan
    Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
    Diabetes Care 35:976-83. 2012
    ..We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity ..
  82. pmc Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion
    Jeroen R Huyghe
    Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
    Nat Genet 45:197-201. 2013
    b>Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes...
  83. pmc SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Invest 109:1125-31. 2002
  84. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003
    ..a FOXO-family transcription factor, influences the rate of ageing of Caenorhabditis elegans in response to insulin/insulin-like growth factor 1 (IGF-I) signalling...
  85. pmc Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila
    Richard C Grandison
    Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, UK
    Nature 462:1061-4. 2009
    ..Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms, and we find that it also ..
  86. pmc The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling
    Peggy P Hsu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 332:1317-22. 2011
    ..We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic ..
  87. ncbi Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan
    Nataliya Libina
    Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 115:489-502. 2003
    In C. elegans, the transcription factor DAF-16 promotes longevity in response to reduced insulin/IGF-1 signaling or germline ablation. In this study, we have asked how different tissues interact to specify the lifespan of the animal...
  88. ncbi AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
    Barbara B Kahn
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 1:15-25. 2005
    ..Complex signaling networks suggest that AMPK may prevent insulin resistance, in part by inhibiting pathways that antagonize insulin signaling...
  89. doi A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets
    Jalal Taneera
    Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmo 20502, Sweden
    Cell Metab 16:122-34. 2012
    ..we identified gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c)...
  90. ncbi An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
    W Brogiolo
    Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    Curr Biol 11:213-21. 2001 Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K.
  91. ncbi Use and abuse of HOMA modeling
    Tara M Wallace
    Oxford Centre for Diabetes, Endocrinology and Metabolism, The Churchill Hospital, Old Road, Oxford OX3 7LJ, U K
    Diabetes Care 27:1487-95. 2004
    Homeostatic model assessment (HOMA) is a method for assessing beta-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations...
  92. pmc Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes
    Anders H Rosengren
    Lund University Diabetes Centre, Department of Clinical Sciences Malmo, Lund University, Malmo, Sweden
    Diabetes 61:1726-33. 2012
    The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown...
  93. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
    Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this...
  94. pmc Increased adipose tissue in male and female estrogen receptor-alpha knockout mice
    P A Heine
    Departments of Veterinary Biosciences and Kinesiology, University of Illinois, Urbana, IL 61802, USA
    Proc Natl Acad Sci U S A 97:12729-34. 2000
    ..Both alphaERKO males and females had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase...
  95. pmc Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance
    Justin I Odegaard
    Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305 5103, USA
    Nature 447:1116-20. 2007
    Obesity and insulin resistance, the cardinal features of metabolic syndrome, are closely associated with a state of low-grade inflammation...
  96. ncbi Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance
    Richard A Miller
    Department of Pathology, Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, MI 48109 0940, USA
    Aging Cell 4:119-25. 2005
    ..Compared with controls, Meth-R mice have significantly lower levels of serum IGF-I, insulin, glucose and thyroid hormone...
  97. ncbi Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
    David A Guertin
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02141, USA
    Dev Cell 11:859-71. 2006
    ..Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3beta, requires mLST8 and rictor...
  98. ncbi Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming
    Anne Maj Samuelsson
    Division of Reproduction and Endocrinology, King s College London, London, UK
    Hypertension 51:383-92. 2008
    ..01). OO skeletal muscle mass (tibialis anterior) was significantly reduced (P<0.01) OO fasting insulin was raised at 3 months and by 6 months fasting plasma glucose was elevated...
  99. pmc Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
    Gilad Twig
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    EMBO J 27:433-46. 2008
    ..autophagy and resulted in the accumulation of oxidized mitochondrial proteins, reduced respiration and impaired insulin secretion...
  100. doi Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
    Evert Kroon
    Novocell, Inc, 3550 General Atomics Ct, San Diego, California 92121, USA
    Nat Biotechnol 26:443-52. 2008
    ..Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human ..
  101. pmc Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo
    Yi Tan
    Chinese American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou, Zhejiang, China
    Diabetes 60:625-33. 2011
    Oxidative stress is implicated in cardiac insulin resistance, a critical risk factor for cardiac failure, but the direct evidence remains missing...

Research Grants70

    Harvey Lodish; Fiscal Year: 2007
    ..which transport membrane associated proteins like GLUT4, secreted proteins where secretion is stimulated by insulin such as ARCP30 (adipocyte complement related protein of 30 kDa-cloned by the PI from a subtractive cDNA library ..
  2. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
    ..Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways. ..
  3. Novel TIRF microscopy analyzing trafficking & signaling at the cell cortex
    Derek Toomre; Fiscal Year: 2009
    ..Consistent with the recovery act's goal, this funding will provide full-time summer employment for 4 undergraduate students and accelerate scientific achievement of the parent DP2 award...
  4. Xenoestrogen regulation of Leydig cells
    ..Akt (protein kinase B) acting in concert with estrogen receptor ER1, epidermal growth factor receptors (EGFR), insulin growth factor-1 receptors (IGF-1R) and mitogen activated protein kinases (MAPK) (Aim II);and, Action of soy ..
  5. Pyruvate Dehydrogenase kinase as Therapeutic Target for Hepatic Steatosis, Obesit
    Robert A Harris; Fiscal Year: 2012
    ..First, down regulation of the expression of PDKs is a critical component of the mechanism by which insulin controls blood glucose...
  6. Sogol Mostoufi-Moab; Fiscal Year: 2016 bone health, body composition, and fat distribution after childhood HSCT, and determine associations with insulin resistance, the metabolic syndrome, and bone deficits. The study has two primary components...
  7. Role of Chromogranin A in Metabolic Syndrome
    Sushil K Mahata; Fiscal Year: 2013
    ..b>Insulin resistance is a central component defining the MS...
  8. Pharmacogenetics of obesity and endocannabinergic modulation (POEM)
    Russell A Wilke; Fiscal Year: 2012
    ..between variation in these candidate genes and obesity and obesity-related metabolic disorders (changes in insulin responsiveness and derangements in lipid homeostasis) in 2209 study subjects from 507 families participating in ..
  9. Autonomic, Endothelial, and Inflammatory Correlates of Sleep Duration
    ..these associations such as autonomic nervous system dysfunction, endothelial dysfunction, inflammation, and insulin resistance have been identified in the setting of sleep disordered breathing (SDB), namely sleep apnea, or in ..
  10. Comprehensive biomarker study to capitalize on existing GWAS in 10K South Asians
    Danish Saleheen; Fiscal Year: 2010
    ..lipoprotein subclasses, oxidized phospholipids, authoantibodies to oxLDL, LpPLA2, sPLA2, myeloperoxidase);(2) insulin resistance and adiposity (insulin, C-peptide, adiponectin, leptin, resistin, liver function enzymes);(3) renal ..
  11. Angiotensin Adrenergic Interactions in the Kidney
    Roland C Blantz; Fiscal Year: 2013
    ..These include 1) reduced NO functional activity, 2) role of AII induced insulin resistance in the kidney (we have shown that acute insulin infusion ameliorates approximately 40-50% of the ..
  12. Qinghua Sun; Fiscal Year: 2015
    ..investigate if air pollution exposure contributes to adiposity and inflammation in adipose tissues that induces insulin resistance and vascular dysfunction, we hypothesize that exposure to fine particulate matter (PM2...
  13. Effective treatment of sleep apnea in prediabetes to reduce cardiometabolic risk
    Esra Tasali; Fiscal Year: 2010
    ..intermediate state between normal glucose tolerance and overt diabetes, characterized by elevated glucose levels, insulin resistance and abnormalities in insulin secretion...
  14. Ang II and Aldosterone Effects on Insulin Resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Decreased insulin sensitivity is a cardinal feature of various pathological conditions such as type 2 diabetes and hypertension...
  15. Ashraf Gorgey; Fiscal Year: 2016
    ..are at a lifelong risk of increasing obesity and several chronic metabolic disorders such as glucose intolerance, insulin resistance and dyslipidemia secondary to deterioration in body composition...
  16. Retinoid and Carotenoid Depletion in Patients at High-Risk for Liver Cancer
    Peter H Gann; Fiscal Year: 2010
    ..For Aim 1 we will test the importance of multiple factors (poor diet, stage of CLD, smoking, insulin resistance, age and race) as independent predictors of serum antioxidant levels...
  17. Role of Txnip in adapting fuel metabolism to nutritional state
    SIMON HUI; Fiscal Year: 2013
    ..Despite having impaired mitochondrial oxidation, TKO mice showed increased insulin/Akt signaling due to decreased amount of active PTEN (reduced form) and were resistance to high fat diet-induced ..
  18. Charles W Wilkinson; Fiscal Year: 2016
    ..Provocative testing is costly, time-consuming, and laborintensive. In addition, the insulin tolerance test (ITT), which is generally considered the gold standard test for both GHD and sAI, requires ..
  19. JAMES RUSSELL SOWERS; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Diminished insulin (INS) sensitivity is a common feature of disease states such as obesity, hypertension and diabetes...
  20. Randal J Kaufman; Fiscal Year: 2014
    ..a disease of world-wide epidemic proportion derived from a failure of beta cells to produce relatively sufficient insulin to maintain euglycemia...
  21. Impact of the P479L Variant in CPT1A on Infant Mortality in Alaska
    David M Koeller; Fiscal Year: 2011
    ..Alterations of energy metabolism resulting from dysregulation of CPT1 affects insulin sensitivity, appetite regulation, and a growing list of other critical functions that are tied to fatty acid ..
  22. Response to and signals of caloric restriction and intermittent feeding regimens
    MARC KOPEL HELLERSTEIN; Fiscal Year: 2010
    ..cell proliferation (mammary, prostate, skin, liver, lymphocytes), adipose tissue dynamics and fat distribution, insulin sensitivity, and vascular smooth muscle cell proliferation...
  23. Role of SCD1 and Dietary Methionine Restriction on Energy Homeostasis
    ERIC PAUL PLAISANCE; Fiscal Year: 2011 applicant): Obesity is associated with a number of metabolic and cardiovascular disease risk factors including insulin resistance, high blood pressure and dysregulation of lipid and glucose metabolism...
  24. Sphingolipid Metabolism in Drosophila Development
    Julie D Saba; Fiscal Year: 2013
    ..understanding endogenous regulators of the AKT pathway is relevant to the vastly important medical problem of insulin- resistance and metabolic syndrome, whereas devising new pharmacological agents to inhibit PI3K/AKT signaling is ..
    Michael J LaMonte; Fiscal Year: 2013
    ..and lower body fat levels will modify the association between Metsyn and periodontal disease;and that greater insulin sensitivity and lower systemic inflammatory are, in part, potential mechanisms through which higher physical ..
    Maureen J Charron; Fiscal Year: 2010
    ..The GLUT4+/- mouse model (G4+/-) represents an example of an `At Risk'individual as male G4+/- mice develop insulin resistance, hypertension and T2DM with age...
  27. Mechanisms of action of ghrelin in muscle and adipose tissue in cancer-related ca
    Jose M Garcia; Fiscal Year: 2013
    ..These changes will be mediated through: a) increases in energy intake, b) activation of insulin-like growth factor-1 (IGF-1)-dependent pathways and c) downregulation of nuclear factor kappa B (NF:B)-dependent ..
  28. Functional Genomics of the Mitochondrial Proteome
    Dennis R Winge; Fiscal Year: 2011
    ..will also be used to determine if oxidative stress and mitochondrial dysfunction will increase the risk for insulin resistance and lipotoxicity...
  29. Genetic and physiological causes of inherited Vascular and Metabolic Diseases
    Arya Mani; Fiscal Year: 2013
    ..tolerance tests in nondiabetic R611C mutation carriers have shown that they are hyperinsulinemic, indicating that insulin resistance is likely the major cause of impaired glucose tolerance in the mutation carriers...
  30. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Impaired insulin signaling in the myocardium may contribute to cardiac dysfunction in obesity, type 2 diabetes and other insulin resistant states...
  31. Norma S Kenyon; Fiscal Year: 2015
    ..islets may limit inflammation, enhance islet revascularization and reduce the number of donors needed to achieve insulin independence...
  32. Donald A McClain; Fiscal Year: 2016
    ..Ferritin also correlates inversely with levels of adiponectin, the insulin sensitizing adipokine...
  33. David A Bernlohr; Fiscal Year: 2014
    ..a variety of loss and gain of function analyses have indicated that oxidative stress is causally linked to insulin resistance but that the molecular mechanisms remain obscure...
  34. Biology and Pathologies of Type V Collagen
    Daniel S Greenspan; Fiscal Year: 2013 adipose tissue, and Col5a3-/- females also have decreased adiposity, accompanied by glucose-intolerance, insulin-resistance, and decreased adipokine levels...
    JERROLD MICHAEL OLEFSKY; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Obesity is the dominant cause of acquired insulin resistance and it is the epidemic of obesity in the United States which is driving the dramatically increasing incidence of Type 2 diabetes...
  36. Judith A James; Fiscal Year: 2016
    ..Multiple sclerosis, rheumatoid arthritis, pediatric arthritis, insulin-dependent diabetes, idiopathic thrombocytopenia and pediatric lupus are other key disease emphases of the ..
  37. Pathobiology of Cystic Fibrosis-Related Diabetes in a Ferret Model
    Zoe Stewart; Fiscal Year: 2013
    ..assess the effectiveness of pancreatic CFTR gene replacement in the CFTR-/- ferrets by evaluating serum glucose, insulin, glucagon, endocrine pancreatic function, and pancreatic duct cell physiology...
    Lisa M Salati; Fiscal Year: 2012
    ..literature has developed that suggests that eating the majority of calories as fat results in the development of insulin resistance and type II diabetes mellitus...
  39. DAVID MATTHEW KELLER; Fiscal Year: 2016
    ..monophosphate (cAMP) second messenger signaling cascade is a key regulator of diverse cellular process such as insulin secretion and energy homeostasis (Seino and Shibasaki, 2005)...
  40. UTPAL BHAGIRATH PAJVANI; Fiscal Year: 2015
    ..research to benefit patients, whether it be through the discovery of a novel pathway in the development of insulin resistance, or application of a known therapeutic agent from cancer biology to the metabolic syndrome...
  41. Thomas L Clemens; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The insulin-like growth factors evolved in lower animalsto enable a wide range of physiological processes including smell, food consumption, metabolism, growth, reproduction and dormancy...
  42. Osteocalcin and Metabolic Risk Factors. The Framingham Study
    Yi Hsiang Hsu; Fiscal Year: 2011
    ..may play a crucial role in endocrine regulation of energy metabolism by enhancing b-cell proliferation, insulin production, insulin sensitivity and adiponectin expression as a feedback loop of Leptin's regulation of ..
  43. W Timothy Garvey; Fiscal Year: 2016
    ..b>Insulin resistance at the level of skeletal muscle is central to the underlying pathogenesis of all these disease ..
  44. Mahin D Maines; Fiscal Year: 2015
    ..Demonstrated functions of BVR include regulation and/or activation of kinases in the insulin/IGF/MAPK/PI3K signaling pathways that regulate glucose uptake, cell growth, apoptosis and stress-response gene ..
  45. John Y L Chiang; Fiscal Year: 2016
    ..provided by applicant): Type II diabetes and obesity are associated with dyslipidemia, hyperglycemia and insulin resistance...
    ANTHONY JUSTIN MUSLIN; Fiscal Year: 2010
    ..Diabetic cardiomyopathy may develop because of the dysfunctional accumulation of lipids in cardiac myocytes. Insulin action is dependent on the activation of an intracellular signaling pathway that stimulates the serine/threonine ..
  47. Parathyroid Hormone & Vitamin D Effects on Salt Sensitivity and Vascular Function
    ANNA LIZA BELEN VALINA TOTH; Fiscal Year: 2010
    ..physiological effects within the vasculature and myocardium such as vasoconstriction, activation of fibroblasts, insulin resistance, dyslipidemia, fat deposition and down regulation of endothelial nitric oxide - all of which plausibly ..
  48. Donald B Jump; Fiscal Year: 2015
    ..Restoration of hepatic Elovl5 activity abrogated high fat diet-induced hyperglycemia, insulin resistance, and fatty liver in 4 days without changing body weight or appetite...
    Jessica A Whiteley; Fiscal Year: 2011
    ..Statistics, 2004). Co-morbid conditions are increasingly seen in obese youth, including insulin resistance, type 2 diabetes, hypertension, obstructive sleep apnea, poor self-esteem, lower health-related ..
  50. Weight Loss &Exercise Effects on Telomere Length in Postmenopausal Women
    ANNE M MCTIERNAN; Fiscal Year: 2012
    ..telomere length and other analytes already measured in the trial: DNA damage repair (COMET), sex hormones, insulin &glucose, inflammation (C-reactive protein, serum amyloid A, interleukin-6), insulin like growth factor 1 and ..
  51. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2012
    ..have indicated that the underlying cause of impaired glucose tolerance caused by LRP6 mutation is impaired insulin sensitivity...
  52. Molecular Mechanism of Protein Kinase Cbeta-Mediated Cholesterol Homeostasis
    Kamal D Mehta; Fiscal Year: 2010
    ..low density lipoprotein (LDL)-cholesterol levels in association with hypertriglyceridemia, abdominal obesity, or insulin resistance...
  53. Surgical amelioration of type 2 diabetes: Hormones, microbiota and mitochondria
    PETER J contact HAVEL; Fiscal Year: 2010
    ..In our current studies, we have demonstrated improved glucose tolerance and insulin sensitivity and a significant (~3 month) delay in the age of diabetes onset in IT compared with sham-operated ..
  54. Robert S Sherwin; Fiscal Year: 2014
    ..Obese adolescents on their path to developing prediabetes/T2DM present with severe peripheral insulin resistance, marked hyperinsulinemia and relatively low leptin levels...
  55. Plant-Derived Estrogens and Cell Proliferation
    Emma Shtivelman; Fiscal Year: 2011
    ..represents a major public health burden because it increases the risk of cardiovascular disease, and promotes insulin resistance and diabetes...
  56. Sex Hormones in Postmenopausal Women in the Diabetes Prevention Program
    Catherine Kim; Fiscal Year: 2012
    ..exogenous hormone only, lack of significant glucose changes, lack of measurement of potential confounders such as insulin homeostasis, or examination only in Caucasians of European ancestry...
    Jarmo Virtamo; Fiscal Year: 2010
    ..of vitamin E and selenium status;carotenoids and other antioxidants;one-carbon metabolism;energy balance, insulin, and growth factors;sex steroids;and genetic variants impacting these exposures...
  58. Ken R Smith; Fiscal Year: 2015
    ..serum cholesterol, glycosylated hemoglobin, dehydroepiandrosterone sulfate (DHEAS &DHEA), fasting glucose and insulin resistance, telomere length, blood pressure, heart rate, grip strength, forced expiratory volume (FEV1), and BMI...
  59. Role of stearoyl CoA desaturase-1 in TLR5 KO mice colitis and metabolic syndrome
    Matam Vijay Kumar; Fiscal Year: 2013
    ..Such low-grade inflammation in TLR5KO mice resulted in hyperglycemia, hyperlipidemia, hyperphagia, insulin resistance, obesity, hepatic steatosis and hypertension, collectively referred to as metabolic syndrome...
  60. RAMON E PARSONS; Fiscal Year: 2016
    ..potentially influence many signaling pathways, perhaps the best understood pathway involving these genes is the insulin/IGF pathway, which is conserved in homo sapiens, c. elegans and drosophila...
  61. Anna Eisenstein; Fiscal Year: 2015 changing blood glucose levels due to reduced responsiveness of tissues to the glucose regulatory hormone, insulin, and/or an insufficient secretion of insulin...
  62. Potential Mechanisms of Glucagon-like peptide-1 in Fatty Liver Disease
    Frank A Anania; Fiscal Year: 2010
    ..b>Insulin resistance is the primary pathophysiologic problem that results in a net accumulation of triglycerides in ..
  63. Metabolic Adapation and Control of Lactation in Humans
    Morey W Haymond; Fiscal Year: 2010
    ..Lactating women have increased insulin sensitivity and increased glucose effectiveness when compared to that of nonlactating women. 2...
  64. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    Mitochondrial Dysfunction and Adipose Insulin Resistance Abstract A variety of animal, cell culture and molecular studies have correlated increased oxidative stress and the accumulation of reactive oxygen species (ROS) such as superoxide ..
    David Hafler; Fiscal Year: 2000
    This proposal will investigate the immunologic mechanisms of tolerization to self antigen in humans with insulin dependent diabetes mellitus (IDDM)...
  66. Insulin Resistance and Adenomas of the Colorectum
    Tim Byers; Fiscal Year: 2003
    There is considerable evidence that insulin and/or insulin-like growth factors (IGFs) can increase risk of colorectal neoplasia...
  67. Insulin Resistance and Adenomas of the Colorectum
    RALPH DAGOSTINO; Fiscal Year: 2003
    There is considerable evidence that insulin and/or insulin-like growth factors (IGFs) can increase risk of colorectal neoplasia...
  68. Role of the insulin/IGF-axis in incident CIN-2+
    Howard D Strickler; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The insulin/insulin-like growth factor (IGF)-axis is a major regulator of cell proliferation/survival, and circulating IGF-axis protein levels are associated with the risk of several solid tumors, ..
    Kieren Mather; Fiscal Year: 2003
    Central obesity/insulin resistance (OB/IR), is associated with a clustering of cardiovascular risk factors...