insulin

Summary

Gene Symbol: insulin
Description: insulin
Alias: IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10, insulin, preproinsulin, proinsulin
Species: human
Products:     insulin

Top Publications

  1. Oda N, Nakai A, Fujiwara K, Imamura S, Fujita T, Hamagishi M, et al. Polymorphisms of the insulin gene among Japanese subjects. Metabolism. 2001;50:631-4 pubmed
    We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%)...
  2. Garin I, Edghill E, Akerman I, Rubio Cabezas O, Rica I, Locke J, et al. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci U S A. 2010;107:3105-10 pubmed publisher
    Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes...
  3. Pettersen E, Skorpen F, Kvaløy K, Midthjell K, Grill V. Genetic heterogeneity in latent autoimmune diabetes is linked to various degrees of autoimmune activity: results from the Nord-Trøndelag Health Study. Diabetes. 2010;59:302-10 pubmed publisher
    ..004 and P = 0.004, respectively). Genetic heterogeneity in LADA is linked to various degrees of autoimmune activity and may be partly distinct from both type 1 and type 2 diabetes. ..
  4. Boguslavsky S, Chiu T, Foley K, Osorio Fuentealba C, Antonescu C, Bayer K, et al. Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles. Mol Biol Cell. 2012;23:4065-78 pubmed publisher
    GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion ..
  5. Steck A, Zhang W, Bugawan T, Barriga K, Blair A, Erlich H, et al. Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?. Diabetes. 2009;58:1028-33 pubmed publisher
    ..Of those, 112 have developed islet autoimmunity (persistent autoantibodies to insulin, GAD65, and/or IA-2), and 47 of these have progressed to type 1 diabetes...
  6. Kuroda A, Rauch T, Todorov I, Ku H, Al Abdullah I, Kandeel F, et al. Insulin gene expression is regulated by DNA methylation. PLoS ONE. 2009;4:e6953 pubmed publisher
    b>Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study...
  7. Støy J, Steiner D, Park S, Ye H, Philipson L, Bell G. Clinical and molecular genetics of neonatal diabetes due to mutations in the insulin gene. Rev Endocr Metab Disord. 2010;11:205-15 pubmed publisher
    ..Recently, mutations in the insulin gene (INS) itself have been identified as another cause of neonatal diabetes...
  8. Ferk P, Perme M, Gersak K. Insulin gene polymorphism in women with polycystic ovary syndrome. J Int Med Res. 2008;36:1180-7 pubmed
    b>Insulin resistance is one of the main characteristics of polycystic ovary syndrome (PCOS) and is probably genetically predisposed...
  9. Colombo C, Porzio O, Liu M, Massa O, Vasta M, Salardi S, et al. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. J Clin Invest. 2008;118:2148-56 pubmed publisher
    ..Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.
  10. Ferron M, Wei J, Yoshizawa T, Del Fattore A, Depinho R, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142:296-308 pubmed publisher
    The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described...

Detail Information

Publications78

  1. Oda N, Nakai A, Fujiwara K, Imamura S, Fujita T, Hamagishi M, et al. Polymorphisms of the insulin gene among Japanese subjects. Metabolism. 2001;50:631-4 pubmed
    We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%)...
  2. Garin I, Edghill E, Akerman I, Rubio Cabezas O, Rica I, Locke J, et al. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci U S A. 2010;107:3105-10 pubmed publisher
    Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes...
  3. Pettersen E, Skorpen F, Kvaløy K, Midthjell K, Grill V. Genetic heterogeneity in latent autoimmune diabetes is linked to various degrees of autoimmune activity: results from the Nord-Trøndelag Health Study. Diabetes. 2010;59:302-10 pubmed publisher
    ..004 and P = 0.004, respectively). Genetic heterogeneity in LADA is linked to various degrees of autoimmune activity and may be partly distinct from both type 1 and type 2 diabetes. ..
  4. Boguslavsky S, Chiu T, Foley K, Osorio Fuentealba C, Antonescu C, Bayer K, et al. Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles. Mol Biol Cell. 2012;23:4065-78 pubmed publisher
    GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion ..
  5. Steck A, Zhang W, Bugawan T, Barriga K, Blair A, Erlich H, et al. Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?. Diabetes. 2009;58:1028-33 pubmed publisher
    ..Of those, 112 have developed islet autoimmunity (persistent autoantibodies to insulin, GAD65, and/or IA-2), and 47 of these have progressed to type 1 diabetes...
  6. Kuroda A, Rauch T, Todorov I, Ku H, Al Abdullah I, Kandeel F, et al. Insulin gene expression is regulated by DNA methylation. PLoS ONE. 2009;4:e6953 pubmed publisher
    b>Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study...
  7. Støy J, Steiner D, Park S, Ye H, Philipson L, Bell G. Clinical and molecular genetics of neonatal diabetes due to mutations in the insulin gene. Rev Endocr Metab Disord. 2010;11:205-15 pubmed publisher
    ..Recently, mutations in the insulin gene (INS) itself have been identified as another cause of neonatal diabetes...
  8. Ferk P, Perme M, Gersak K. Insulin gene polymorphism in women with polycystic ovary syndrome. J Int Med Res. 2008;36:1180-7 pubmed
    b>Insulin resistance is one of the main characteristics of polycystic ovary syndrome (PCOS) and is probably genetically predisposed...
  9. Colombo C, Porzio O, Liu M, Massa O, Vasta M, Salardi S, et al. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. J Clin Invest. 2008;118:2148-56 pubmed publisher
    ..Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.
  10. Ferron M, Wei J, Yoshizawa T, Del Fattore A, Depinho R, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142:296-308 pubmed publisher
    The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described...
  11. Boesgaard T, Pruhova S, Andersson E, Cinek O, Obermannova B, Lauenborg J, et al. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY). BMC Med Genet. 2010;11:42 pubmed publisher
    ..One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS) in a Danish MODYX family...
  12. Serre Beinier V, Bosco D, Zulianello L, Charollais A, Caille D, Charpantier E, et al. Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression. Hum Mol Genet. 2009;18:428-39 pubmed publisher
    Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-..
  13. Russo L, Iafusco D, Brescianini S, Nocerino V, Bizzarri C, Toni S, et al. Permanent diabetes during the first year of life: multiple gene screening in 54 patients. Diabetologia. 2011;54:1693-701 pubmed publisher
    ..The aim of this study was to investigate the genetic aetiology of permanent diabetes mellitus with onset in the first 12 months of age...
  14. Bonfanti R, Colombo C, Nocerino V, Massa O, Lampasona V, Iafusco D, et al. Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies. Diabetes Care. 2009;32:123-5 pubmed publisher
    ..and at 6 years 8 months of age, respectively, we identified the mutation G(B8)S and a novel mutation in the preproinsulin signal peptide (A(Signal23)S)...
  15. Cervin C, Lyssenko V, Bakhtadze E, Lindholm E, Nilsson P, Tuomi T, et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes. 2008;57:1433-7 pubmed publisher
    ..8%) and type 1 diabetic subjects (43.3%). LADA shares genetic features with both type 1 (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes. ..
  16. Smyth D, Plagnol V, Walker N, Cooper J, Downes K, Yang J, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767-77 pubmed publisher
    ..These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases. ..
  17. Meur G, Simon A, Harun N, Virally M, Dechaume A, Bonnefond A, et al. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention. Diabetes. 2010;59:653-61 pubmed publisher
    Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neonatal or early-infancy diabetes...
  18. Sano H, Peck G, Kettenbach A, Gerber S, Lienhard G. Insulin-stimulated GLUT4 protein translocation in adipocytes requires the Rab10 guanine nucleotide exchange factor Dennd4C. J Biol Chem. 2011;286:16541-5 pubmed publisher
    b>Insulin-stimulated translocation of the glucose transporter GLUT4 to the cell surface in fat and muscle cells is the basis for insulin-stimulated glucose transport...
  19. Jensen M, Hansen B, De Meyts P, Schäffer L, Ursø B. Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J Biol Chem. 2007;282:35179-86 pubmed
    Recently, single chain peptides have been designed that target the insulin receptor and mimic insulin action...
  20. Mook Kanamori D, Miranda Geelhoed J, Steegers E, Witteman J, Hofman A, Moll H, et al. Insulin gene variable number of tandem repeats is not associated with weight from fetal life until infancy: the Generation R Study. Eur J Endocrinol. 2007;157:741-8 pubmed
    The aim of this study was to examine whether the insulin gene variable number of tandem repeats (INS VNTR) is associated with growth patterns in fetal life and infancy...
  21. Molven A, Ringdal M, Nordbø A, Raeder H, Støy J, Lipkind G, et al. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008;57:1131-5 pubmed publisher
    Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes...
  22. Støy J, Edghill E, Flanagan S, Ye H, Paz V, Pluzhnikov A, et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007;104:15040-4 pubmed
    ..The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin ..
  23. Liu M, Hodish I, Haataja L, Lara Lemus R, Rajpal G, Wright J, et al. Proinsulin misfolding and diabetes: mutant INS gene-induced diabetes of youth. Trends Endocrinol Metab. 2010;21:652-9 pubmed publisher
    ..dominant Mutant INS-gene Induced Diabetes of Youth (MIDY) syndrome, but most missense mutations affecting proinsulin folding produce MIDY...
  24. Polak M, Dechaume A, Cave H, Nimri R, Crosnier H, Sulmont V, et al. Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group. Diabetes. 2008;57:1115-9 pubmed publisher
    Permanent neonatal diabetes (PND) is defined by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life...
  25. Park S, Ye H, Steiner D, Bell G. Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted. Biochem Biophys Res Commun. 2010;391:1449-54 pubmed publisher
    Mutations in the preproinsulin protein that affect processing of preproinsulin to proinsulin or lead to misfolding of proinsulin are associated with diabetes...
  26. Chiu T, Patel N, Shaw A, Bamburg J, Klip A. Arp2/3- and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells. Mol Biol Cell. 2010;21:3529-39 pubmed publisher
    GLUT4 vesicles are actively recruited to the muscle cell surface upon insulin stimulation...
  27. Raile K, O Connell M, Galler A, Werther G, Kühnen P, Krude H, et al. Diabetes caused by insulin gene (INS) deletion: clinical characteristics of homozygous and heterozygous individuals. Eur J Endocrinol. 2011;165:255-60 pubmed publisher
    Mutations of the preproinsulin gene (INS) account for both permanent neonatal diabetes (PND) and adult-onset diabetes...
  28. Plagnol V, Howson J, Smyth D, Walker N, Hafler J, Wallace C, et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 2011;7:e1002216 pubmed publisher
    ..Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A). ..
  29. Støy J, Greeley S, Paz V, Ye H, Pastore A, Skowron K, et al. Diagnosis and treatment of neonatal diabetes: a United States experience. Pediatr Diabetes. 2008;9:450-9 pubmed publisher
    ..The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age...
  30. Edghill E, Flanagan S, Patch A, Boustred C, Parrish A, Shields B, et al. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008;57:1034-42 pubmed
    b>Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND)...
  31. Ahamed A, Unnikrishnan A, Pendsey S, Nampoothiri S, Bhavani N, Praveen V, et al. Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report. JOP. 2008;9:715-8 pubmed
    ..It has been hypothesized that these mutations disrupt the folding of the proinsulin molecule and result in a misfolded protein or retention of the protein in the endoplasmic reticulum, resulting ..
  32. Hermann R, Lipponen K, Kiviniemi M, Kakko T, Veijola R, Simell O, et al. Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes. Diabetologia. 2006;49:1198-208 pubmed
    ..of islet cell autoantibodies, and individuals found to be positive were tested for autoantibodies against insulin (IAA), glutamic acid decarboxylase and islet antigen-2 (n = 574; mean follow-up time 4.9 years)...
  33. Laine A, Hermann R, Knip M, Simell O, Akerblom H, Ilonen J. The human leukocyte antigen genotype has a modest effect on the insulin gene polymorphism-associated susceptibility to type 1 diabetes in the Finnish population. Tissue Antigens. 2004;63:72-4 pubmed
    In addition to the known human leukocyte antigen (HLA)-associated risk, polymorphisms of insulin gene region show association with type 1 diabetes...
  34. Calvo R, Telleria D, Sancho J, San Millan J, Escobar Morreale H. Insulin gene variable number of tandem repeats regulatory polymorphism is not associated with hyperandrogenism in Spanish women. Fertil Steril. 2002;77:666-8 pubmed
    To determine if the insulin gene variable number of tandem repeats (VNTR) regulatory polymorphism is associated with hyperandrogenism in a population of Spanish women. Controlled clinical study. Tertiary institutional hospital...
  35. Saltiel A, Kahn C. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;414:799-806 pubmed
    ..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, ..
  36. Adkins R, Krushkal J, Klauser C, Magann E, Morrison J, Somes G. Association between small for gestational age and paternally inherited 5' insulin haplotypes. Int J Obes (Lond). 2008;32:372-80 pubmed
    To test the association between small for gestational age and polymorphisms in the insulin gene in newborns and their mothers, as well as the effect of the parental transmission of haplotypes...
  37. Collinet M, Berthelon M, Benit P, Laborde K, Desbuquois B, Munnich A, et al. Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping. Eur J Pediatr. 1998;157:456-60 pubmed
    ..is a rare genetic disorder characterized by point mutations in the insulin gene which impair the conversion of proinsulin to insulin...
  38. Larson J, Miranker A. The mechanism of insulin action on islet amyloid polypeptide fiber formation. J Mol Biol. 2004;335:221-31 pubmed
    ..islet amyloid polypeptide (IAPP), is a hormone involved in glucose metabolism and is normally co-secreted with insulin by the beta-cells of the pancreas...
  39. Goodge K, Hutton J. Translational regulation of proinsulin biosynthesis and proinsulin conversion in the pancreatic beta-cell. Semin Cell Dev Biol. 2000;11:235-42 pubmed
    ..components, principally insulin and the enzymes PC1, PC2, and CPH involved in the proteolytic conversion of proinsulin to insulin...
  40. Davies J, Kawaguchi Y, Bennett S, Copeman J, Cordell H, Pritchard L, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature. 1994;371:130-6 pubmed
    We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis...
  41. Bell G, Swain W, Pictet R, Cordell B, Goodman H, Rutter W. Nucleotide sequence of a cDNA clone encoding human preproinsulin. Nature. 1979;282:525-7 pubmed
  42. Yano H, Kitano N, Morimoto M, Polonsky K, Imura H, Seino Y. A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). J Clin Invest. 1992;89:1902-7 pubmed
    ..high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials...
  43. Marchand L, Polychronakos C. Evaluation of polymorphic splicing in the mechanism of the association of the insulin gene with diabetes. Diabetes. 2007;56:709-13 pubmed
    The association of type 1 diabetes with the insulin gene (IDDM2 locus) has been mapped to a short haplotype encompassing two single nucleotide polymorphisms (SNPs) in perfect linkage disequilibrium (r(2) = 1) with each other and with the ..
  44. Hermann R, Laine A, Veijola R, Vahlberg T, Simell S, Lähde J, et al. The effect of HLA class II, insulin and CTLA4 gene regions on the development of humoral beta cell autoimmunity. Diabetologia. 2005;48:1766-75 pubmed
    ..We analysed the effect of HLA class II, insulin (INS; -23 HphI variant) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4 [+49 and CT60]) genes on the ..
  45. Oyer P, Cho S, Peterson J, Steiner D. Studies on human proinsulin. Isolation and amino acid sequence of the human pancreatic C-peptide. J Biol Chem. 1971;246:1375-86 pubmed
  46. Vafiadis P, Ounissi Benkalha H, Palumbo M, Grabs R, Rousseau M, Goodyer C, et al. Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes. J Clin Endocrinol Metab. 2001;86:3705-10 pubmed
    Type 1 diabetes results from autoimmune destruction of the insulin-producing pancreatic beta cells. The insulin gene (INS) is also expressed in human thymus, an ectopic expression site likely involved in immune tolerance...
  47. Ho G, Melman A, Liu S, Li M, Yu H, Negassa A, et al. Polymorphism of the insulin gene is associated with increased prostate cancer risk. Br J Cancer. 2003;88:263-9 pubmed
    High insulin levels are linked with increased cancer risk, including prostate cancer...
  48. Perez de Nanclares G, Bilbao J, Calvo B, Vitoria J, Vazquez F, Castano L. 5'-Insulin gene VNTR polymorphism is specific for type 1 diabetes: no association with celiac or Addison's disease. Ann N Y Acad Sci. 2003;1005:319-23 pubmed
    The VNTR region located at the 5'-end of the insulin gene on chromosome 11p15...
  49. Julier C, Hyer R, Davies J, Merlin F, Soularue P, Briant L, et al. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature. 1991;354:155-9 pubmed
    A class of alleles at the VNTR (variable number of tandem repeat) locus in the 5' region of the insulin gene (INS) on chromosome 11p is associated with increased risk of insulin-dependent diabetes mellitus (IDDM), but family studies have ..
  50. Given B, Mako M, Tager H, Baldwin D, Markese J, Rubenstein A, et al. Diabetes due to secretion of an abnormal insulin. N Engl J Med. 1980;302:129-35 pubmed
    ..8 to 9.4 mmol per liter). Plasma proinsulin, glucagon, growth hormone, and cortisol levels were normal; insulin antibodies and insulin-receptor antibodies ..
  51. Sanger F. Chemistry of insulin; determination of the structure of insulin opens the way to greater understanding of life processes. Science. 1959;129:1340-4 pubmed
  52. Adamson K, Cheetham T, Kendall Taylor P, Seckl J, Pearce S. The role of the IDDM2 locus in the susceptibility of UK APS1 subjects to type 1 diabetes mellitus. Int J Immunogenet. 2007;34:17-21 pubmed
    ..However, alleles of a variable number tandem repeat (VNTR) 5' of the insulin gene are known to influence the development of T1D in the general, non-APS1 population...
  53. Liu M, Li Y, Cavener D, Arvan P. Proinsulin disulfide maturation and misfolding in the endoplasmic reticulum. J Biol Chem. 2005;280:13209-12 pubmed
    Upon nonreducing Tris-Tricine-urea-SDS-PAGE, newly synthesized proinsulin from pancreatic islets of normal rodents forms a band fast mobility representing the native disulfide isomer, which is efficiently secreted...
  54. Jensen R, Gilliam L, Torn C, Landin Olsson M, Karlsson F, Palmer J, et al. Multiple factors affect the loss of measurable C-peptide over 6 years in newly diagnosed 15- to 35-year-old diabetic subjects. J Diabetes Complications. 2007;21:205-13 pubmed
    ..36-0.58). This study identified autoantibody status, gender, and baseline C-peptide levels as factors that will be useful for predicting the disease course of 15- to 35-year-old diabetic individuals. ..
  55. Todd J, Walker N, Cooper J, Smyth D, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857-64 pubmed
    ..Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten. ..
  56. Hong D, Ahmad A, Fink A. Fibrillation of human insulin A and B chains. Biochemistry. 2006;45:9342-53 pubmed
    Human insulin, which consists of disulfide cross-linked A and B polypeptide chains, readily forms amyloid fibrils under slightly destabilizing conditions...
  57. Hay C, Ferguson L, Docherty K. ATF-2 stimulates the human insulin promoter through the conserved CRE2 sequence. Biochim Biophys Acta. 2007;1769:79-91 pubmed
    The insulin promoter contains a number of dissimilar cis-acting regulatory elements that bind a range of tissue specific and ubiquitous transcription factors...
  58. Sabater L, Ferrer Francesch X, Sospedra M, Caro P, Juan M, Pujol Borrell R. Insulin alleles and autoimmune regulator (AIRE) gene expression both influence insulin expression in the thymus. J Autoimmun. 2005;25:312-8 pubmed
    It is well established that the polymorphisms at the 5' of the insulin gene (IDDM2) confers susceptibility to type 1 diabetes, probably by modifying the level of insulin expression in the thymus that in turn influences immunological ..
  59. Laine A, Holmberg H, Nilsson A, Ortqvist E, Kiviniemi M, Vaarala O, et al. Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations. Dis Markers. 2007;23:139-45 pubmed
    We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI...
  60. Bennett S, Lucassen A, Gough S, Powell E, Undlien D, Pritchard L, et al. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat Genet. 1995;9:284-92 pubmed
    The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5...
  61. Warren Perry M, Manley S, Ostrega D, Polonsky K, Mussett S, Brown P, et al. A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. J Clin Endocrinol Metab. 1997;82:1629-31 pubmed
    ..male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma insulin level 29 pmol/L(-1) (..
  62. Le Stunff C, Fallin D, Schork N, Bougneres P. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Nat Genet. 2000;26:444-6 pubmed
    In millions of people, obesity leads to type 2 diabetes (T2D; also known as non-insulin-dependent diabetes mellitus)...
  63. Osada H, Seki K, Sekiya S. Genetic variations within the insulin gene region are associated with accelerated fetal growth. Tohoku J Exp Med. 2007;212:27-34 pubmed
    ..to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus...
  64. Whittingham J, Scott D, Chance K, Wilson A, Finch J, Brange J, et al. Insulin at pH 2: structural analysis of the conditions promoting insulin fibre formation. J Mol Biol. 2002;318:479-90 pubmed
    When insulin solutions are subjected to acid, heat and agitation, the normal pattern of insulin assembly (dimers-->tetramers-->hexamers) is disrupted; the molecule undergoes conformational changes allowing it to follow an ..
  65. Ong K, Petry C, Barratt B, Ring S, Cordell H, Wingate D, et al. Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain. Diabetes. 2004;53:1128-33 pubmed
    Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size...
  66. Liu M, Hodish I, Rhodes C, Arvan P. Proinsulin maturation, misfolding, and proteotoxicity. Proc Natl Acad Sci U S A. 2007;104:15841-6 pubmed
    As a tool to explore proinsulin (PI) trafficking, a human PI cDNA has been constructed with GFP fused within the C peptide...
  67. Stene L, Thorsby P, Berg J, Rønningen K, Undlien D, Joner G. The relation between size at birth and risk of type 1 diabetes is not influenced by adjustment for the insulin gene (-23HphI) polymorphism or HLA-DQ genotype. Diabetologia. 2006;49:2068-73 pubmed
    Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth...
  68. Abderrahmani A, Niederhauser G, Favre D, Abdelli S, Ferdaoussi M, Yang J, et al. Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells. Diabetologia. 2007;50:1304-14 pubmed
    ..Prolonged incubation with human oxidised LDL particles led to a reduction in preproinsulin expression levels, whereas the insulin level was preserved in the presence of native LDL-cholesterol...
  69. Shoelson S, Fickova M, Haneda M, Nahum A, Musso G, Kaiser E, et al. Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution. Proc Natl Acad Sci U S A. 1983;80:7390-4 pubmed
    Using information gained from (i) the relative HPLC retention of an abnormal insulin present in the serum of a hyperinsulinemic diabetic patient and (ii) the loss of an Mbo II restriction site in one of the patient's insulin gene alleles,..
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