DIABETES AND ENDOCRINOLOGY RESEARCH CENTER

Summary

Principal Investigator: Domenico Accili
Abstract: DESCRIPTION (provided by applicant): The Columbia University Diabetes Research Center was established in May 2003. As the focus of diabetes research at the largest academic medical center in the largest U.S. metropolitan area, the Columbia DRC promotes interactions among an outstanding research base, integrating basic and translational diabetes research with existing institutional centers of excellence in obesity, atherosclerosis, neurobiology, and cardiovascular biology. The DRC fosters translation of basic research advances, clinical training, epidemiology, and-through its partnership with the Berrie Diabetes Center-encourages diabetes related philanthropy. The Biomedical Research Base is comprised of 84 NIH-, ADA- or JDRF-funded investigators at Columbia, and 7 at sister institutions in New York City. The DRC supports core facilities in (A) Genomics;(B) Hormone &Metabolite;(E) Histopathology;(F) Mouse Phenotyping;and (G) Flow Cytometry. Additionally, the DRC makes available funding for young investigators through a pilot/feasibility grant program (P&F), and provides established scientists in other research areas at Columbia University and in neighboring institutions with the opportunity and support to enter the diabetes field through this program. The DRC supports program enrichment activities, designed to increase the awareness of diabetes research in the scientific/academic community at Columbia University;it also promotes interactions with academic institutions in the greater New York area. An administrative Core provides overall logistical support, financial oversight and integration of research efforts, shared core facilities and P&F program administration. During the past funding cycle, the DRC has endeavored to advance NIDDK's mission in diabetes by: (I) raising awareness of and interest in advanced clinical and basic diabetes research at Columbia University and in New York City;(ii) enhancing training and other diabetes-related educational opportunities for students, fellows, academic and community-based physicians;(///) attracting new investigators to diabetes research;{iv) providing state-of-the-art core facilities to enhance research of DRC members and contribute to the development of innovative methods for diabetes research and care;(v) fostering a collegial academic environment to facilitate information exchange within the institution and with other DRCs;(w) providing impetus to translate basic science discoveries into clinical care and community initiatives to improve the health of people with diabetes;and (wV) leveraging NIDDK resources with local and national philanthropic and diabetes advocacy organizations to integrate and expand P&F grants, as well as training and educational programs.
Funding Period: 2003-05-01 - 2018-01-31
more information: NIH RePORT

Top Publications

  1. pmc Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells
    Shouhong Xuan
    Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 285:41044-50. 2010
  2. pmc Proatherogenic abnormalities of lipid metabolism in SirT1 transgenic mice are mediated through Creb deacetylation
    Li Qiang
    Naomi Berrie Diabetes Center, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 14:758-67. 2011
  3. pmc Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice
    Ning Kon
    Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 287:5102-11. 2012
  4. pmc Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 15:65-74. 2012
  5. pmc Common variants in the CD36 gene are associated with oral fat perception, fat preferences, and obesity in African Americans
    Kathleen L Keller
    Department of Research Medicine, New York Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Obesity (Silver Spring) 20:1066-73. 2012
  6. pmc FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis
    Aruna Kode
    Department of Medicine, Division of Endocrinology, Columbia University, New York, New York 10032, USA
    J Biol Chem 287:8757-68. 2012
  7. pmc FGF21 and the second coming of PPARγ
    Li Qiang
    Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Cell 148:397-8. 2012
  8. pmc Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively deacetylated alleles of Foxo1 gene
    Li Qiang
    Berrie Diabetes Center and Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 287:13944-51. 2012
  9. pmc FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 15:372-81. 2012
  10. pmc Generation of functional insulin-producing cells in the gut by Foxo1 ablation
    Chutima Talchai
    Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA
    Nat Genet 44:406-12, S1. 2012

Research Grants

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013

Detail Information

Publications122 found, 100 shown here

  1. pmc Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells
    Shouhong Xuan
    Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 285:41044-50. 2010
    ..The insulin and IGF pathways appear to control β cell functions independently and selectively...
  2. pmc Proatherogenic abnormalities of lipid metabolism in SirT1 transgenic mice are mediated through Creb deacetylation
    Li Qiang
    Naomi Berrie Diabetes Center, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 14:758-67. 2011
    ..We propose that SirT1-dependent Creb deacetylation regulates the balance between glucose and lipid metabolism, integrating fasting signals...
  3. pmc Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice
    Ning Kon
    Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 287:5102-11. 2012
    ..These findings underscore an important role of ARF-BP1 in maintaining β-cell homeostasis in aging mice and reveal that the stability of p53 is critically regulated by ARF-BP1 in vivo...
  4. pmc Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 15:65-74. 2012
    ..We propose that generation of 12α-hydroxylated products of BA metabolism represents a signaling mechanism linking hepatic lipid abnormalities with type 2 diabetes, and a treatment target for this condition...
  5. pmc Common variants in the CD36 gene are associated with oral fat perception, fat preferences, and obesity in African Americans
    Kathleen L Keller
    Department of Research Medicine, New York Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Obesity (Silver Spring) 20:1066-73. 2012
    ..001), but only 2 D/D individuals were tested, so this finding needs replication. This is the first study to demonstrate an association between common variants in CD36 and fat ingestive behaviors in humans...
  6. pmc FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis
    Aruna Kode
    Department of Medicine, Division of Endocrinology, Columbia University, New York, New York 10032, USA
    J Biol Chem 287:8757-68. 2012
    ..Taken together these observations demonstrate that FoxO1 and ATF4 cooperate in osteoblasts to regulate glucose homeostasis...
  7. pmc FGF21 and the second coming of PPARγ
    Li Qiang
    Department of Medicine and Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Cell 148:397-8. 2012
    ..Does this new property improve FGF21's fledgling clinical prospects or endorse a clinical resuscitation of PPARγ agonists?..
  8. pmc Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively deacetylated alleles of Foxo1 gene
    Li Qiang
    Berrie Diabetes Center and Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 287:13944-51. 2012
    ..The data indicate that FoxO1 deacetylation can promote vascular endothelial changes conducive to atherosclerotic plaque formation...
  9. pmc FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 15:372-81. 2012
    ..The data demonstrate that FoxO inhibition in endothelial cells has the potential to mediate wide-ranging therapeutic benefits for diabetes-associated cardiovascular disease...
  10. pmc Generation of functional insulin-producing cells in the gut by Foxo1 ablation
    Chutima Talchai
    Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA
    Nat Genet 44:406-12, S1. 2012
    ..The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes...
  11. pmc Generation of Nkx2.2:lacZ mice using recombination-mediated cassette exchange technology
    Luis Arnés
    Department of Genetics and Development, Columbia University, New York, New York, USA
    Genesis 50:612-24. 2012
    ..In the CNS of Nkx2.2(lacZ/lacZ) embryos, LacZ-expressing cells within the ventral P3 progenitor domain display different migration properties depending on the developmental stage and their respective differentiation potential...
  12. pmc FoxO1 target Gpr17 activates AgRP neurons to regulate food intake
    Hongxia Ren
    Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell 149:1314-26. 2012
    ..These effects are absent in Agrp-Foxo1 knockouts, suggesting that pharmacological modulation of this pathway has therapeutic potential to treat obesity...
  13. pmc Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ
    Li Qiang
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell 150:620-32. 2012
    ..We propose that SirT1-dependent Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import...
  14. pmc Neurofunctional imaging of β-cell dynamics
    P E Harris
    Division of Endocrinology, Department of Medicine, The Naomi Berrie Diabetes Center and Columbia University College of Physicians and Surgeons, New York, NY, USA
    Diabetes Obes Metab 14:91-100. 2012
    ..Many of these same circuits operate in the central nervous system and can be visualized by molecular imaging. We discuss how these techniques might be applied to measuring the dynamics of β-cell function in real time...
  15. pmc Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming
    James B Papizan
    Department of Genetics and Development, Institute of Human Nutrition, Columbia University, New York 10032, USA
    Genes Dev 25:2291-305. 2011
    ..2(TNmut/TNmut) mutant mice reverts the β-to-α-cell conversion, indicating that the repressor activities of Nkx2.2 on the methylated Arx promoter in β cells are the primary regulatory events required for maintaining β-cell identity...
  16. pmc Dissociation of the glucose and lipid regulatory functions of FoxO1 by targeted knockin of acetylation-defective alleles in mice
    Alexander S Banks
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 14:587-97. 2011
    ..Thus, acetylation inactivates FoxO1 during nutrient excess whereas deacetylation selectively potentiates FoxO1 activity, protecting against excessive catabolism during nutrient deprivation...
  17. pmc Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny
    Jill S Carmody
    Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, New York, USA
    Obesity (Silver Spring) 19:492-9. 2011
    ..Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny...
  18. pmc Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin-induced nephropathy in mice
    Natalia Papeta
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 120:4055-64. 2010
    ..These findings implicate mtDNA damage in the development of ADR toxicity and identify Prkdc as a MDDS modifier gene and a component of the mitochondrial genome maintenance pathway...
  19. pmc Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling
    George Stratigopoulos
    Division of Molecular Genetics, Department of Pediatrics and Naomi Berrie Diabetes Center, Columbia University, New York, New York 10032, USA
    J Biol Chem 286:2155-70. 2011
    ....
  20. pmc Reconstitution of insulin action in muscle, white adipose tissue, and brain of insulin receptor knock-out mice fails to rescue diabetes
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 286:9797-804. 2011
    ..The broader implication of our findings is that diabetes treatment should not necessarily target the same tissues that are responsible for disease pathogenesis...
  21. pmc Diabetes in mice with selective impairment of insulin action in Glut4-expressing tissues
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 60:700-9. 2011
    ..We hypothesized that diabetes is the result of impaired insulin signaling in all Glut4-expressing tissues...
  22. pmc Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism
    Yoshihiro Yoshikawa
    Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    J Bone Miner Res 26:2012-25. 2011
    ....
  23. pmc Responses of gut microbiota to diet composition and weight loss in lean and obese mice
    Yann Ravussin
    Division of Molecular Genetics and Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Obesity (Silver Spring) 20:738-47. 2012
    ..Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat...
  24. pmc Identification of the nephropathy-susceptibility locus HIVAN4
    Sindhuri Prakash
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Am Soc Nephrol 22:1497-504. 2011
    ..In summary, these data identify HIVAN4 as a major quantitative trait locus for nephropathy and a transregulator of Nphs2. Furthermore, similar selective breeding strategies may help identify further susceptibility loci...
  25. pmc Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner
    Utpal B Pajvani
    Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 17:961-7. 2011
    ..The data identify a heretofore unknown metabolic function of Notch and suggest that Notch inhibition is beneficial in diabetes treatment, in part by helping to offset excessive FoxO1-driven hepatic glucose production...
  26. pmc Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression
    Teresa L Mastracci
    Department of Genetics and Development, Russ Berrie Medical Pavilion, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA
    Dev Biol 359:1-11. 2011
    ..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells...
  27. pmc Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas
    Salma Begum
    Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA
    Gene Expr Patterns 11:476-83. 2011
    ..These dynamic changes in the expression pattern of these transcription factors lay the foundation for investigation of potential roles in pancreas development...
  28. pmc Fat discrimination: a phenotype with potential implications for studying fat intake behaviors and obesity
    Lisa C H Liang
    Department of Research Medicine, New York Obesity Research Center, St Luke s Roosevelt Hospital, Columbia University College of Physicians and Surgeons, NY, NY 10025, USA
    Physiol Behav 105:470-5. 2012
    ..53; p<0.01). If these results are replicated, fat discrimination may serve as clinical research tool to identify participants who are at risk for obesity and other chronic diseases due to increased fat intake...
  29. pmc Homozygosity for an allele encoding deacetylated FoxO1 protects macrophages from cholesterol-induced inflammation without increasing apoptosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Arterioscler Thromb Vasc Biol 31:2920-8. 2011
    ..We sought to identify the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this process...
  30. pmc FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin
    Aruna Kode
    Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 122:3490-503. 2012
    ..These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation...
  31. 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...
  32. pmc Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis
    Shouhong Xuan
    Department of Genetics and Development, Columbia University, New York, New York 10032, USA
    J Clin Invest 122:3516-28. 2012
    ....
  33. pmc Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability
    Utpal B Pajvani
    Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 19:1054-60. 2013
    ..These data identify Notch as a therapeutically actionable branch point of metabolic signaling at which Akt activation in the liver can be uncoupled from hepatosteatosis. ..
  34. pmc Blunted refeeding response and increased locomotor activity in mice lacking FoxO1 in synapsin-Cre-expressing neurons
    Hongxia Ren
    Berrie Diabetes Center, New York, New York
    Diabetes 62:3373-83. 2013
    ....
  35. pmc Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, New York
    Diabetes 62:4184-91. 2013
    ..These findings suggest a role for 12α-hydroxylated BAs in metabolic abnormalities in the natural history of T2D and raise the possibility of developing insulin-sensitizing therapeutics based on manipulations of BA composition. ..
  36. pmc The immune cells in adipose tissue
    A W Ferrante
    Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA
    Diabetes Obes Metab 15:34-8. 2013
    ..Here we review the modulation of immune cell populations in adipose tissue and discuss regulatory processes implicated in controlling the interface between metabolism and immunologic function. ..
  37. pmc A differential dielectric affinity glucose sensor
    Xian Huang
    Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA
    Lab Chip 14:294-301. 2014
    ..This sensor can potentially be used clinically as a subcutaneously implanted continuous monitoring device in diabetic patients. ..
  38. pmc Limited recovery of β-cell function after gastric bypass despite clinical diabetes remission
    Roxanne Dutia
    Department of Medicine, St Luke s Roosevelt Hospital Center, New York, NY
    Diabetes 63:1214-23. 2014
    ..This impairment can be rescued by oral glucose stimulation, suggesting that RYGBP leads to an important gastrointestinal effect, critical for improved β-cell function after surgery. ..
  39. pmc Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation
    Xiaoyuan Xu
    Department of Medicine, Naomi Berrie Diabetes Center, Columbia University, New York, NY 07043, USA
    Cell Metab 18:816-30. 2013
    ..These data argue that ATMs contribute quantitatively to the development of obesity-induced inflammation but also serve an important role in lipid trafficking independent of their inflammatory phenotype. ..
  40. pmc Periodontal infection and cardiorespiratory fitness in younger adults: results from continuous national health and nutrition examination survey 1999-2004
    Ashley Thai
    Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America
    PLoS ONE 9:e92441. 2014
    ..Our objective was to study the association between clinical measures of periodontal infection and cardiorespiratory fitness levels among a population-based sample of younger adults...
  41. pmc Probing behavioral responses to food: development of a food-specific go/no-go task
    Theresa Teslovich
    Sackler Institute, Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA Electronic address
    Psychiatry Res 219:166-70. 2014
    ....
  42. pmc ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis
    Kazuhisa Watanabe
    Naomi Berrie Diabetes Center and Department of Pediatrics, Columbia University, New York, New York, United States of America
    PLoS ONE 8:e67234. 2013
    ..Given these reciprocal interactions, and the relatively extended time-course over which these studies were conducted, we cannot assign causal primacy to either the effects on hepatic lipid homeostasis or ER stress responses. ..
  43. pmc Fat cell size and adipokine expression in relation to gender, depot, and metabolic risk factors in morbidly obese adolescents
    Yiying Zhang
    Division of Molecular Genetics, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, USA Naomi Berrie Diabetes Center, Columbia University, College of Physicians and Surgeons, New York, USA
    Obesity (Silver Spring) 22:691-7. 2014
    ..To understand the regulation of adipocyte size and adipokine expression in relation to gender, anatomic location, adiposity, and metabolic risk factors in adolescents with morbid obesity...
  44. pmc Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population
    Luis Arnés
    Department of Genetics and Development, Columbia University, New York, New York, USA
    PLoS ONE 7:e52026. 2012
    ....
  45. pmc Continuous monitoring of glucose in subcutaneous tissue using microfabricated differential affinity sensors
    Xian Huang
    Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA
    J Diabetes Sci Technol 6:1436-44. 2012
    ....
  46. pmc The role of lipids in the control of autophagy
    Claudia Dall'Armi
    Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA
    Curr Biol 23:R33-45. 2013
    ..This review summarizes this progress and highlights the role of specific lipids in the various steps of macroautophagy, including the signaling processes underlying macroautophagy initiation, autophagosome biogenesis and maturation...
  47. pmc Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Diabetes 62:1478-89. 2013
    ..The findings are consistent with a model in which excessive, rather than reduced, insulin signaling in ECs predisposes to systemic insulin resistance, prompting a reevaluation of current approaches to insulin sensitization...
  48. pmc Molecular basis for the regulation of islet beta cell mass in mice: the role of E-cadherin
    N Wakae-Takada
    Department of Pediatrics, Columbia University, New York, NY, USA
    Diabetologia 56:856-66. 2013
    ..Here, we tested the hypothesis that increasing levels of E-cadherin during islet formation mediate the decline in beta cell proliferation rate by contributing to a reduction of nuclear β-catenin and D-cyclins...
  49. pmc Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas
    Teresa L Mastracci
    Department of Genetics and Development, Russ Berrie Medical Pavilion, Columbia University, New York, New York, USA
    PLoS Genet 9:e1003278. 2013
    ..These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage...
  50. pmc Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center, 1150 St Nicholas Ave, Russ Berrie Pavilion Room 238, NY 10032, USA
    Circ Res 112:992-1003. 2013
    ..Increased neutrophil and monocyte counts are often associated with an increased risk of atherosclerosis, but their relationship to insulin sensitivity is unknown...
  51. pmc Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor
    Virendra K Chaudhri
    Department of Biochemistry, Weill Cornell Medical College New York, New York, NY 10065, USA
    Mol Cancer Res 11:579-92. 2013
    ..In sum, our data suggest that increased autophagy may account for metabolic differences between CAFs and NFs and may play additional as yet undetermined roles in lung cancer...
  52. pmc Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children
    Michael Rosenbaum
    Pediatrics Department, New York Presbyterian Hospital Columbia University Medical Center, New York, New York, USA
    Obesity (Silver Spring) 21:2081-90. 2013
    ....
  53. pmc Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and β-cell Function in type 2 diabetic patients
    Clifton Jackness
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Diabetes 62:3027-32. 2013
    ..Likewise, changes in fasting glucose and fructosamine levels were similar. Based on these data, VLCD improves insulin sensitivity and β-cell function just as well as RYGB in the short term. ..
  54. pmc Obesity accelerates Helicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response
    Russell E Ericksen
    Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore
    Gut 63:385-94. 2014
    ..To investigate the role of obesity-associated inflammation and immune modulation in gastric carcinogenesis during Helicobacter-induced chronic gastric inflammation...
  55. pmc iPSC-derived β cells model diabetes due to glucokinase deficiency
    Haiqing Hua
    The New York Stem Cell Foundation Laboratory, New York, New York, USA
    J Clin Invest 123:3146-53. 2013
    ..Our results demonstrate that iPSC-derived β cells reflect β cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on β cell function. ..
  56. pmc CCR2 modulates inflammatory and metabolic effects of high-fat feeding
    Stuart P Weisberg
    Department of Medicine, Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 116:115-24. 2006
    ....
  57. pmc Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance
    Stephanie O Harbers
    Departments of Microbiology and Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, USA
    J Clin Invest 117:1361-9. 2007
    ..Thus, we show that autoreactive antibody can potently enhance the activation of effector T cells in response to cross-presented self antigen, thereby contributing to T cell-mediated autoimmunity...
  58. ncbi Fc gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses
    Dharmesh D Desai
    Department of Medicine and Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Immunol 178:6217-26. 2007
    ..Thus, FcgammaRIIB can contribute to peripheral tolerance maintenance by inhibiting DC activation alone or by also limiting processing of exogenously acquired Ag...
  59. ncbi Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice
    Hua V Lin
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Diabetes 56:1969-76. 2007
    ..Adiponectin increases insulin sensitivity and contributes to insulin's indirect effects on hepatic glucose production...
  60. ncbi Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells
    Nicole A Sherry
    Department of Immunobiology, Yale University, New Haven, CT 06520, USA
    Endocrinology 148:5136-44. 2007
    ..This combinatorial approach may be useful in treatment of patients with new-onset T1DM...
  61. pmc A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
    Tadahiro Kitamura
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    J Clin Invest 117:2477-85. 2007
    ..Notch/Foxo1 cooperation may integrate environmental cues through Notch with metabolic cues through Foxo1 to regulate progenitor cell maintenance and differentiation...
  62. ncbi Obesity-induced inflammation: a metabolic dialogue in the language of inflammation
    A W Ferrante
    Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA
    J Intern Med 262:408-14. 2007
    ..Defining the molecular and cellular components of obesity-induced inflammation offers the potential of identifying therapeutic targets that can ameliorate the complications associated with obesity...
  63. ncbi Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates
    Rajan Murthy
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Eur J Nucl Med Mol Imaging 35:790-7. 2008
    ..To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [(11)C]-DTBZ in humans...
  64. pmc Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion
    Esther van de Wall
    Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 12461, USA
    Endocrinology 149:1773-85. 2008
    ....
  65. pmc Potential role of increased matrix metalloproteinase-2 (MMP2) transcription in impaired adipogenesis in type 2 diabetes mellitus
    Severine G Dubois
    Health and Performance Enhancement Division, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA
    Biochem Biophys Res Commun 367:725-8. 2008
    ..32, p=0.03). We conclude that early steps of adipogenesis may be impaired in T2DM independently of obesity due, in part, to an upregulation of the MMP2 transcription...
  66. pmc Mechanisms of disease: using genetically altered mice to study concepts of type 2 diabetes
    Derek LeRoith
    Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L Levy Place, Atran AB4 36, Box 1055, New York, NY 10029 6574, USA
    Nat Clin Pract Endocrinol Metab 4:164-72. 2008
    ....
  67. pmc Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate
    Jose E Galgani
    Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA 70808, USA
    Diabetes 57:841-5. 2008
    ....
  68. pmc Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4
    Jesko Koehnke
    Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Structure 16:410-21. 2008
    ..These results raise the possibility that beta-NRX insertion sequence 4 may function in roles independent of neuroligin binding...
  69. pmc Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine
    Anthony Raffo
    Department of Medicine, BB 20 06, Columbia University Medical Center, 650 West 168th Street, New York, New York 10032, USA
    J Endocrinol 198:41-9. 2008
    ..Together, these data suggest that VMAT2 regulates in vivo glucose homeostasis and insulin production, most likely via its role in vesicular transport and storage of monoamines in beta-cells...
  70. ncbi Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus
    Koichiro Azuma
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Am J Physiol Endocrinol Metab 293:E435-42. 2007
    ..In summary, T2DM, compared with similarly obese nondiabetic men and women, is associated with less leg FM and greater trunk FM and hepatic fat...
  71. pmc Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes
    BLANDINE LAFERRERE
    Obesity Research Center, St Luke s Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111 Amsterdam Ave, New York, NY 10025, USA
    Diabetes Care 30:1709-16. 2007
    ..We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP...
  72. ncbi Expansion and redifferentiation of adult human pancreatic islet cells
    Limor Ouziel-Yahalom
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
    Biochem Biophys Res Commun 341:291-8. 2006
    ..These methods may allow transplantation of functional islet cells from single donors into multiple recipients...
  73. ncbi Allelic variation on chromosome 5 controls beta-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice
    Na Luo
    Institute of Human Nutrition, Department of Pediatrics, Columbia University, New York, New York 10032, USA
    Endocrinology 147:2287-95. 2006
    ..Finally, we offer arguments that production of multiple incipient congenic lines is an economical alternative to the production of speed congenic strains...
  74. pmc Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance
    Haruka Okamoto
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 116:775-82. 2006
    ..We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion...
  75. ncbi Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
    Tadahiro Kitamura
    Department of Medicine, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Nat Med 12:534-40. 2006
    ..Thus, FoxO1 represents a shared component of pathways integrating food intake and peripheral metabolism...
  76. pmc Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model
    Fabiola Souza
    Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 116:1506-13. 2006
    ..These studies suggest that PET-based quantitation of VMAT2 receptors provides a noninvasive measurement of BCM that could be used to study the pathogenesis of diabetes and to monitor therapeutic interventions...
  77. ncbi An ancestral haplotype defines susceptibility to doxorubicin nephropathy in the laboratory mouse
    Zongyu Zheng
    Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Am Soc Nephrol 17:1796-800. 2006
    ..These data demonstrate that susceptibility to DOX nephropathy represents a founder mutation in the laboratory mouse. Haplotype analysis can be used for identification of the DOXNPH gene and prediction of strain susceptibility pattern...
  78. pmc Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism
    Michihiro Matsumoto
    Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 116:2464-72. 2006
    ....
  79. ncbi Drug insight: New immunomodulatory therapies in type 1 diabetes
    Simona Cernea
    Columbia University, New York, NY, USA
    Nat Clin Pract Endocrinol Metab 2:89-98. 2006
    ..Ultimately, preservation and even improvement in beta-cell mass is the goal of therapy. The means needed to achieve this will depend on the timing and mechanisms of the immune intervention and might require combinations of agents...
  80. pmc Visualizing pancreatic beta-cell mass with [11C]DTBZ
    Norman Ray Simpson
    Department of Radiology, Columbia University Medical School, New York, NY 10032, USA
    Nucl Med Biol 33:855-64. 2006
    ....
  81. ncbi Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas
    Fabiola Souza
    Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
    Curr Med Chem 13:2761-73. 2006
    ..We review the current understanding of the pathogenesis and evaluation of diabetes, as well as experimental approaches to assessing beta-cell mass...
  82. ncbi Effects of autoimmunity and immune therapy on beta-cell turnover in type 1 diabetes
    Nicole A Sherry
    Section of Immunobiology, Yale University, 300 Cedar St, Room S155B, New Haven, CT 06520, USA
    Diabetes 55:3238-45. 2006
    ..Correction of the beta-cell loss in type 1 diabetes will, therefore, require strategies that target both the immunologic and cellular mechanisms that destroy and maintain beta-cell mass...
  83. ncbi Genes for diabetic nephropathy: sweet prospects on the horizon
    H H Karnib
    Department of Medicine, American University of Beirut, Beirut, Lebanon
    Kidney Int 71:94-6. 2007
    ..Osterholm et al. provide further evidence that a gene on chromosome 3q confers susceptibility to this diabetic complication...
  84. ncbi Analysis of compensatory beta-cell response in mice with combined mutations of Insr and Irs2
    Jane J Kim
    Deparment of Pediatrics, University of California, San Diego, California, USA
    Am J Physiol Endocrinol Metab 292:E1694-701. 2007
    ..The eventual failure of compensatory insulin secretion suggests that a comprehensive treatment of beta-cell dysfunction in type 2 diabetes should positively affect both aspects of beta-cell physiology...
  85. pmc The double life of Irs
    Rebecca A Haeusler
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10027, USA
    Cell Metab 8:7-9. 2008
    ..Two studies in this issue (Kubota et al., 2008; Dong et al., 2008) on the insulin-signaling adaptors Irs1 and Irs2 prompt a critical reappraisal of the physiology of fasting and of the integrated control of hepatic insulin action...
  86. pmc Positional cloning of "Lisch-Like", a candidate modifier of susceptibility to type 2 diabetes in mice
    Marija Dokmanovic-Chouinard
    Naomi Berrie Diabetes Center, Columbia University, New York, New York, USA
    PLoS Genet 4:e1000137. 2008
    ..D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes...
  87. pmc Novel hypoglycemic dihydropyridones serendipitously discovered from O- versus C-alkylation in the synthesis of VMAT2 antagonists
    Yuli Xie
    Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
    Bioorg Med Chem Lett 18:5111-4. 2008
    ..Several analogs were designed and synthesized. A preliminary structure activity relationship (SAR) showed that the dihydropyridone scaffold is required for the activity...
  88. pmc Divergent regulation of energy expenditure and hepatic glucose production by insulin receptor in agouti-related protein and POMC neurons
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 59:337-46. 2010
    ..We have shown that mice with hypothalamic deficiency (L1) of insulin receptors (InsRs) fail to regulate hepatic glucose production (HGP) in response to insulin...
  89. pmc Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes
    Jeanine B Albu
    Department of Medicine, St Luke s Roosevelt Hospital Center, Columbia University, New York, New York, USA
    Diabetes 59:627-33. 2010
    ....
  90. pmc FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice
    Marie Therese Rached
    Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    J Clin Invest 120:357-68. 2010
    ....
  91. pmc C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis
    Amrom E Obstfeld
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 59:916-25. 2010
    ..This suggests that a myeloid cell population is recruited to the liver in obesity and contributes to nonalcoholic fatty liver disease...
  92. pmc FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts
    Marie Therese Rached
    Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Cell Metab 11:147-60. 2010
    ..These results identify FoxO1 as a crucial regulator of osteoblast physiology and provide a direct mechanistic link between oxidative stress and the regulation of bone remodeling...
  93. pmc Six-Minute Walk Test demonstrates motor fatigue in spinal muscular atrophy
    J Montes
    SMA Clinical Research Center, Department of Neurology, Columbia University, 180 Ft Washington Ave, 5th Floor, New York, NY 10032, USA
    Neurology 74:833-8. 2010
    ..The Six-Minute Walk Test (6MWT) is an objective, easily administered, and standardized evaluation of functional exercise capacity that has been proven reliable in other neurologic disorders and in children...
  94. pmc Pomc-expressing progenitors give rise to antagonistic neuronal populations in hypothalamic feeding circuits
    Stephanie L Padilla
    Institute of Human Nutrition, Columbia University, New York, New York, USA
    Nat Med 16:403-5. 2010
    ..Moreover, nearly one quarter of the mature NPY+ cell population shares a common progenitor with POMC+ cells...
  95. pmc Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis
    C F Zizola
    Department of Medicine and Institute of Human Nutrition, Columbia University, New York, New York 10032, USA
    Mol Cell Biol 30:3412-20. 2010
    ..In conclusion, CRBP-I is a cytosolic protein specifically expressed in preadipocytes that regulates adipocyte differentiation in part by affecting PPAR gamma activity...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..