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Gene Review

INS  -  insulin

Homo sapiens

Synonyms: IDDM, IDDM1, IDDM2, ILPR, IRDN, ...
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Disease relevance of INS


Psychiatry related information on INS

  • Long-term effects of leisure time physical activity on risk of insulin resistance and impaired glucose tolerance, allowing for body weight history, in Danish men [5].
  • The localization of TH to the highly polymorphic INS locus provides four new restriction fragment length polymorphisms which should help determine rapidly whether defects in TH are responsible for bipolar affective disorder in the Old Order Amish and other populations [6].
  • During the 31-year follow-up survey of this genetically homogeneous birth cohort, IR was assessed by 'Qualitative Insulin Sensitivity Check Index' (QUICKI), and severity of depressive symptoms by 'Hopkins' Symptom Checklist-25' (HSCL-25) [7].
  • These polymorphisms were investigated for their possible association with Alzheimer's disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism [8].
  • Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study [9].

High impact information on INS


Chemical compound and disease context of INS


Biological context of INS

  • The insulin minisatellite (INS VNTR) associates with susceptibility to a variety of diseases [19].
  • One is equivalent to the mouse Igf2-P0 transcript, whereas the two others (INSIGF long and short) originate from the upstream INS gene that alternatively splices to downstream IGF2 exons [20].
  • The relevance of the insulin gene (INS) variable number tandem repeat (VNTR) polymorphism to indexes of body size and adult obesity is inconclusive [1].
  • These results indicate that -23HphI and IVS-69 are the most important INS variants affecting pre-mRNA splicing and suggest that -23HphI+/- is a common functional single nucleotide polymorphism at IDDM2 [21].
  • We show that IVS1-6A/T (-23HphI+/-) is a key INS variant that influences alternative splicing of intron 1 through differential recognition of its 3' splice site [21].

Anatomical context of INS

  • The insulin gene (INS) is also expressed in human thymus, an ectopic expression site likely involved in immune tolerance [22].
  • The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously [23].
  • This thymus-specific defect in Igf2 expression may explain both the absence of central tolerance to INS-secreting beta cells and the lymphopenia (including lack of regulatory RT6(+) T cells) in diabetes-prone BB rats [24].
  • In this study, we have assessed the role of PTP1B in the insulin sensitivity of skeletal muscle under physiological and insulin-resistant conditions [14].
  • Peroxisome Proliferator-Activated Receptor {alpha} Improves Pancreatic Adaptation to Insulin Resistance in Obese Mice and Reduces Lipotoxicity in Human Islets [25].

Associations of INS with chemical compounds

  • Serum insulin (INS) levels were studied following an oral glucose load [26].
  • A variable number of tandem repeats (VNTR) polymorphism at the human INS 5'-flanking region consisting of three distinct allele classes has been shown to influence the tissue-specific expression of INS and the insulin-like growth factor 2 (IGF-2) [27].
  • Polymorphism of INS VNTR is associated with glutamic acid decarboxylase antibodies and postprandial C-peptide in patients with onset of diabetes after 35 years of age [4].
  • There were no differences (P>0.05) between F and UF horses for the plasma concentrations of CORT (69+/-14 versus 76+/-23mug/dL), INS (7.2+/-3.5 versus 7.1+/-1.8muIU/mL) or GLU (90+/-6 versus 86+/-7mg/dL) [28].
  • The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component [15].
  • In response to elevated glucose, pre-mRNA species increased within 60 min, whereas increases in mature mRNA did not occur until 48 h, suggesting that measurement of mature mRNA species does not accurately reflect the acute transcriptional response of the insulin gene to glucose [29].

Physical interactions of INS

  • OBJECTIVE: Insulin-like growth factor (IGF-I) and IGF binding protein-3 (IGFBP-3) are GH-dependent and their concentrations have been used in the diagnosis of GH deficiency [30].
  • Half-maximal displacement of 125I-labelled somatomedin C binding occurred at an unlabelled somatomedin C concentration of 0.7 nmol/l. Insulin competed with 125I-labelled somatomedin for binding to this receptor, but 150-fold more insulin was required for half-maximal displacement [31].
  • The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC) [32].
  • These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase [33].
  • We identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is disrupted by high salt concentrations [34].
  • To understand the molecular basis of the recognition and unfolding of insulin by IDE, we determined a 2.6-A resolution insulin-bound IDE structure [35].

Regulatory relationships of INS


Other interactions of INS


Analytical, diagnostic and therapeutic context of INS


  1. INS VNTR class genotype and indexes of body size and obesity: population-based studies of 7,999 middle-aged men and women. Sandhu, M.S., Heude, B., Young, E.H., Luben, R., Luan, J., Khaw, K.T., Todd, J., Wareham, N.J. Diabetes (2005) [Pubmed]
  2. Polymorphism of the insulin gene is associated with increased prostate cancer risk. Ho, G.Y., Melman, A., Liu, S.M., Li, M., Yu, H., Negassa, A., Burk, R.D., Hsing, A.W., Ghavamian, R., Chua, S.C. Br. J. Cancer (2003) [Pubmed]
  3. Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings. Sánchez-Corona, J., Flores-Martínez, S.E., Machorro-Lazo, M.V., Galaviz-Hernández, C., Morán-Moguel, M.C., Perea, F.J., Mújica-López, K.I., Vargas-Ancona, L., Laviada-Molina, H.A., Fernández, V., Pardío, J., Arroyo, P., Barrera, H., Hanson, R.L. Diabetes Res. Clin. Pract. (2004) [Pubmed]
  4. Polymorphism of INS VNTR is associated with glutamic acid decarboxylase antibodies and postprandial C-peptide in patients with onset of diabetes after 35 years of age. Matejková-Behanová, M., Vanková, M., Hill, M., Kucera, P., Cinek, O., Andel, M., Bendlová, B. Physiological research / Academia Scientiarum Bohemoslovaca. (2004) [Pubmed]
  5. Long-term effects of leisure time physical activity on risk of insulin resistance and impaired glucose tolerance, allowing for body weight history, in Danish men. Berentzen, T., Petersen, L., Pedersen, O., Black, E., Astrup, A., Sørensen, T.I. Diabet. Med. (2007) [Pubmed]
  6. Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11. O'Malley, K.L., Rotwein, P. Nucleic Acids Res. (1988) [Pubmed]
  7. Depressive symptoms and insulin resistance in young adult males: results from the Northern Finland 1966 birth cohort. Timonen, M., Rajala, U., Jokelainen, J., Kein??nen-Kiukaanniemi, S., Meyer-Rochow, V.B., R??s??nen, P. Mol. Psychiatry (2006) [Pubmed]
  8. Polymorphism in the peroxisome proliferator-activated receptor alpha gene influences the risk for Alzheimer's disease. Brune, S., Kölsch, H., Ptok, U., Majores, M., Schulz, A., Schlosser, R., Rao, M.L., Maier, W., Heun, R. Journal of neural transmission (Vienna, Austria : 1996) (2003) [Pubmed]
  9. Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study. Bell, R.A., Mayer-Davis, E.J., Martin, M.A., D'Agostino, R.B., Haffner, S.M. Diabetes Care (2000) [Pubmed]
  10. Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity. Le Stunff, C., Fallin, D., Bougnères, P. Nat. Genet. (2001) [Pubmed]
  11. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Le Stunff, C., Fallin, D., Schork, N.J., Bougnères, P. Nat. Genet. (2000) [Pubmed]
  12. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. Cline, G.W., Petersen, K.F., Krssak, M., Shen, J., Hundal, R.S., Trajanoski, Z., Inzucchi, S., Dresner, A., Rothman, D.L., Shulman, G.I. N. Engl. J. Med. (1999) [Pubmed]
  13. Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. Troglitazone and Exogenous Insulin Study Group. Schwartz, S., Raskin, P., Fonseca, V., Graveline, J.F. N. Engl. J. Med. (1998) [Pubmed]
  14. Protein-Tyrosine Phosphatase 1B-Deficient Myocytes Show Increased Insulin Sensitivity and Protection Against Tumor Necrosis Factor-{alpha}-Induced Insulin Resistance. Nieto-Vazquez, I., Fernández-Veledo, S., de Alvaro, C., Rondinone, C.M., Valverde, A.M., Lorenzo, M. Diabetes (2007) [Pubmed]
  15. Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. Gram, D.X., Ahrén, B., Nagy, I., Olsen, U.B., Brand, C.L., Sundler, F., Tabanera, R., Svendsen, O., Carr, R.D., Santha, P., Wierup, N., Hansen, A.J. Eur. J. Neurosci. (2007) [Pubmed]
  16. Islet cell differentiation in liver by combinatorial expression of transcription factors Neurogenin-3, BETA2, and RIPE3b1. Song, Y.D., Lee, E.J., Yashar, P., Pfaff, L.E., Kim, S.Y., Jameson, J.L. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  17. Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women. Bonanni, B., Johansson, H., Gandini, S., Guerrieri-Gonzaga, A., Torrisi, R., Sandri, M.T., Cazzaniga, M., Mora, S., Robertson, C., Lien, E.A., Decensi, A. Breast Cancer Res. Treat. (2001) [Pubmed]
  18. Neuroendocrinology/Endocrinology: Insulin sensitivity in streptozotocin-induced diabetic rats treated with different doses of 17{beta}-oestradiol or progesterone. Ordóñez, P., Moreno, M., Alonso, A., Fernández, R., Díaz, F., González, C. Exp. Physiol. (2007) [Pubmed]
  19. Structural analysis of insulin minisatellite alleles reveals unusually large differences in diversity between Africans and non-Africans. Stead, J.D., Jeffreys, A.J. Am. J. Hum. Genet. (2002) [Pubmed]
  20. Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human. Monk, D., Sanches, R., Arnaud, P., Apostolidou, S., Hills, F.A., Abu-Amero, S., Murrell, A., Friess, H., Reik, W., Stanier, P., Constância, M., Moore, G.E. Hum. Mol. Genet. (2006) [Pubmed]
  21. Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2? Královicová, J., Gaunt, T.R., Rodriguez, S., Wood, P.J., Day, I.N., Vorechovsky, I. Diabetes (2006) [Pubmed]
  22. Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes. Vafiadis, P., Ounissi-Benkalha, H., Palumbo, M., Grabs, R., Rousseau, M., Goodyer, C.G., Polychronakos, C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  23. Immunohistochemical localization of insulin-like growth factor 1 and 2 in the endocrine pancreas of rat, dog, and man, and their coexistence with classical islet hormones. Maake, C., Reinecke, M. Cell Tissue Res. (1993) [Pubmed]
  24. Role of the thymus in the development of tolerance and autoimmunity towards the neuroendocrine system. Geenen, V., Brilot, F. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  25. Peroxisome Proliferator-Activated Receptor {alpha} Improves Pancreatic Adaptation to Insulin Resistance in Obese Mice and Reduces Lipotoxicity in Human Islets. Lalloyer, F., Vandewalle, B., Percevault, F., Torpier, G., Kerr-Conte, J., Oosterveer, M., Paumelle, R., Fruchart, J.C., Kuipers, F., Pattou, F., Fiévet, C., Staels, B. Diabetes (2006) [Pubmed]
  26. Growth in children with craniopharyngioma following surgery. Tiulpakov, A.N., Mazerkina, N.A., Brook, C.G., Hindmarsh, P.C., Peterkova, V.A., Gorelyshev, S.K. Clin. Endocrinol. (Oxf) (1998) [Pubmed]
  27. The insulin gene VNTR polymorphism in Alzheimer's disease: results of a pilot study. Majores, M., Kölsch, H., Bagli, M., Ptok, U., Kockler, M., Becker, K., Rao, M.L., Maier, W., Heun, R. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  28. Plasma leptin, ghrelin and adiponectin concentrations in young fit racehorses versus mature unfit standardbreds. Gordon, M.E., McKeever, K.H., Betros, C.L., Manso Filho, H.C. Vet. J. (2007) [Pubmed]
  29. Glucose regulation of insulin gene transcription and pre-mRNA processing in human islets. Evans-Molina, C., Garmey, J.C., Ketchum, R., Brayman, K.L., Deng, S., Mirmira, R.G. Diabetes (2007) [Pubmed]
  30. Evaluation of free insulin-like growth factor-I measurement on the diagnosis and follow-up treatment of growth hormone-deficient adult patients. Musolino, N.R., Da Cunha Neto, M.B., Marino Júnior, R., Giannella-Neto, D., Bronstein, M.D. Clin. Endocrinol. (Oxf) (1999) [Pubmed]
  31. Autocrine tumour growth regulation by somatomedin C: an in-vitro model. Pavelić, K., Vrbanec, D., Marusić, S., Levanat, S., Cabrijan, T. J. Endocrinol. (1986) [Pubmed]
  32. The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Hochberg, Z., Hertz, P., Colin, V., Ish-Shalom, S., Yeshurun, D., Youdim, M.B., Amit, T. Metab. Clin. Exp. (1992) [Pubmed]
  33. Oral insulin-mimetic compounds that act independently of insulin. García-Vicente, S., Yraola, F., Marti, L., González-Muñoz, E., García-Barrado, M.J., Cantó, C., Abella, A., Bour, S., Artuch, R., Sierra, C., Brandi, N., Carpéné, C., Moratinos, J., Camps, M., Palacín, M., Testar, X., Gumà, A., Albericio, F., Royo, M., Mian, A., Zorzano, A. Diabetes (2007) [Pubmed]
  34. PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase. Sancak, Y., Thoreen, C.C., Peterson, T.R., Lindquist, R.A., Kang, S.A., Spooner, E., Carr, S.A., Sabatini, D.M. Mol. Cell (2007) [Pubmed]
  35. Molecular basis of catalytic chamber-assisted unfolding and cleavage of human insulin by human insulin-degrading enzyme. Manolopoulou, M., Guo, Q., Malito, E., Schilling, A.B., Tang, W.J. J. Biol. Chem. (2009) [Pubmed]
  36. Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. London, S.J., Yuan, J.M., Travlos, G.S., Gao, Y.T., Wilson, R.E., Ross, R.K., Yu, M.C. J. Natl. Cancer Inst. (2002) [Pubmed]
  37. Prolactin and growth hormone responses to hypoglycemia in patients with rheumatoid arthritis and ankylosing spondylitis. Rovensky, J., Imrich, R., Malis, F., Zlnay, M., Macho, L., Koska, J., Vigas, M. J. Rheumatol. (2004) [Pubmed]
  38. Insulin resistance induced by high glucose and high insulin precedes insulin receptor substrate 1 protein depletion in human adipocytes. Renström, F., Burén, J., Svensson, M., Eriksson, J.W. Metab. Clin. Exp. (2007) [Pubmed]
  39. Alpha 1,3-fucosyltransferase-VII regulates the signaling molecules of the insulin receptor pathway. Wang, Q.Y., Zhang, Y., Chen, H.J., Shen, Z.H., Chen, H.L. FEBS J. (2007) [Pubmed]
  40. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. Ma, J., Pollak, M.N., Giovannucci, E., Chan, J.M., Tao, Y., Hennekens, C.H., Stampfer, M.J. J. Natl. Cancer Inst. (1999) [Pubmed]
  41. Postprandial glucagon-like peptide-1 (GLP-1) response is positively associated with changes in neuronal activity of brain areas implicated in satiety and food intake regulation in humans. Pannacciulli, N., Le, D.S., Salbe, A.D., Chen, K., Reiman, E.M., Tataranni, P.A., Krakoff, J. Neuroimage (2007) [Pubmed]
  42. Ethnicity, insulin resistance, and inflammatory adipokines in women at high and low risk for vascular disease. Silha, J.V., Nyomba, B.L., Leslie, W.D., Murphy, L.J. Diabetes Care (2007) [Pubmed]
  43. Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: the data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study. Fumeron, F., Péan, F., Driss, F., Balkau, B., Tichet, J., Marre, M., Grandchamp, B. Diabetes Care (2006) [Pubmed]
  44. Tumor Necrosis Factor-{alpha} Induces Intestinal Insulin Resistance and Stimulates the Overproduction of Intestinal Apolipoprotein B48-Containing Lipoproteins. Qin, B., Qiu, W., Avramoglu, R.K., Adeli, K. Diabetes (2007) [Pubmed]
  45. Relationship of Androgens to Insulin Resistance and Chronic Inflammation in Morbidly Obese Premenopausal Women: Studies before and after Vertical Banded Gastroplasty. Kopp, H.P., Krzyzanowska, K., Schernthaner, G.H., Kriwanek, S., Schernthaner, G. Obesity surgery : the official journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. (2006) [Pubmed]
  46. Plasticity of human adipose stem cells to perform adipogenic and endothelial differentiation. Wosnitza, M., Hemmrich, K., Groger, A., Gräber, S., Pallua, N. Differentiation (2007) [Pubmed]
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