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Gene Review

INSIG1  -  insulin induced gene 1

Homo sapiens

Synonyms: CL-6, CL6, INSIG-1, Insulin-induced gene 1 protein, MGC1405
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Disease relevance of INSIG1

  • Small interfering RNA (siRNA) inhibition was used to test the significance of INSIG1 for gene expression in human Huh7 hepatoma cells [1].
  • INSIG1 and p41-Arc are known to be involved in cellular differentiation and morphology, respectively, and it was suggested that their reduced expressions might be involved in gastric cancer development or progression [2].
  • In control ZDF (fa/fa) rats infected with adenovirus containing the beta-galactosidase (beta-gal) cDNA, triacylglycerols in the liver and plasma rose steeply whereas the insig-infected rats exhibited substantial attenuation of the increase in hepatic steatosis and hyperlipidemia [3].
  • The mRNA of endogenous insig-1, but not -2a and -2b, was higher in the fatty livers of untreated obese ZDF (fa/fa) rats compared with controls, but the elevation was not sufficient to block the approximately 3-fold increase in SREBP-1c expression and activity [3].
  • Insulin-induced hypoglycemia also occurred during treatment of hyperkalemia (eight patients) or during hyperglycemia related to total parenteral nutrition (six patients) [4].

Psychiatry related information on INSIG1


High impact information on INSIG1


Chemical compound and disease context of INSIG1


Biological context of INSIG1


Anatomical context of INSIG1

  • By 5-aza-2'-deoxycytidine treatment of 5 cell lines with the methylation of the edge, partial restoration of INSIG1 expression was detected only in 2 of them [2].
  • INSIG1 expression was upregulated at the transcriptional level in rat regenerating liver and induced in a model of murine adipocyte differentiation, suggesting that INSIG1 may play a role in growth and differentiation of tissues involved in metabolic control [15].
  • Insig-1 is an intrinsic protein of the endoplasmic reticulum (ER) that regulates the proteolytic processing of membrane-bound sterol regulatory element-binding proteins (SREBPs), transcription factors that activate the synthesis of cholesterol and fatty acids in mammalian cells [16].
  • The data indicate that short segments at the N and C termini of Insig-1 face the cytosol [16].
  • These results provide formal genetic proof for the essential role of Insig-1 in feedback control of lipid synthesis in cultured cells [14].

Associations of INSIG1 with chemical compounds


Physical interactions of INSIG1


Regulatory relationships of INSIG1


Other interactions of INSIG1


Analytical, diagnostic and therapeutic context of INSIG1


  1. Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration. Krapivner, S., Chernogubova, E., Ericsson, M., Ahlbeck-Glader, C., Hamsten, A., van 't Hooft, F.M. Diabetologia (2007) [Pubmed]
  2. Reduced expression of the insulin-induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers. Kaneda, A., Kaminishi, M., Nakanishi, Y., Sugimura, T., Ushijima, T. Int. J. Cancer (2002) [Pubmed]
  3. Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats. Takaishi, K., Duplomb, L., Wang, M.Y., Li, J., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Hypoglycemia in hospitalized patients. Causes and outcomes. Fischer, K.F., Lees, J.A., Newman, J.H. N. Engl. J. Med. (1986) [Pubmed]
  5. Insulin-induced hypoglycemia and panic attacks. Schweizer, E., Winokur, A., Rickels, K. The American journal of psychiatry. (1986) [Pubmed]
  6. The effect of insulin-induced hypoglycaemia on gastrointestinal motility in man. Fellows, I.W., Evans, D.F., Bennett, T., Macdonald, I.A., Clark, A.G., Bloom, S.R. Clin. Sci. (1987) [Pubmed]
  7. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Yang, T., Espenshade, P.J., Wright, M.E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J.L., Brown, M.S. Cell (2002) [Pubmed]
  8. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Song, B.L., Sever, N., DeBose-Boyd, R.A. Mol. Cell (2005) [Pubmed]
  9. Mechanism of insulin resistance associated with liver cirrhosis. Müller, M.J., Willmann, O., Rieger, A., Fenk, A., Selberg, O., Lautz, H.U., Bürger, M., Balks, H.J., von zur Mühlen, A., Schmidt, F.W. Gastroenterology (1992) [Pubmed]
  10. Is physiologic sympathoadrenal catecholamine release exocytotic in humans? Takiyyuddin, M.A., Cervenka, J.H., Sullivan, P.A., Pandian, M.R., Parmer, R.J., Barbosa, J.A., O'Connor, D.T. Circulation (1990) [Pubmed]
  11. Hypophysiotropic hormone testing in a patient with hypothalamic hypopituitarism. Feldman, A., Bloomgarden, Z.T. Am. J. Med. (1986) [Pubmed]
  12. Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone. Tack, C.J., Ong, M.K., Lutterman, J.A., Smits, P. Diabetologia (1998) [Pubmed]
  13. Neuroendocrine sources of chromogranin-A in normal man: clues from selective stimulation of endocrine glands. Takiyyuddin, M.A., Cervenka, J.H., Pandian, M.R., Stuenkel, C.A., Neumann, H.P., O'Connor, D.T. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  14. Isolation of mutant cells lacking Insig-1 through selection with SR-12813, an agent that stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Sever, N., Lee, P.C., Song, B.L., Rawson, R.B., Debose-Boyd, R.A. J. Biol. Chem. (2004) [Pubmed]
  15. Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene. Peng, Y., Schwarz, E.J., Lazar, M.A., Genin, A., Spinner, N.B., Taub, R. Genomics (1997) [Pubmed]
  16. Membrane topology of human insig-1, a protein regulator of lipid synthesis. Feramisco, J.D., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (2004) [Pubmed]
  17. The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP. Janowski, B.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. Insulin generates free radicals in human fibroblasts ex vivo by a protein kinase C-dependent mechanism, which is inhibited by pravastatin. Ceolotto, G., Papparella, I., Lenzini, L., Sartori, M., Mazzoni, M., Iori, E., Franco, L., Gallo, A., de Kreutzenberg, S.V., Tiengo, A., Pessina, A.C., Avogaro, A., Semplicini, A. Free Radic. Biol. Med. (2006) [Pubmed]
  19. Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of Insig-1. Lee, J.N., Ye, J. J. Biol. Chem. (2004) [Pubmed]
  20. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Sever, N., Yang, T., Brown, M.S., Goldstein, J.L., DeBose-Boyd, R.A. Mol. Cell (2003) [Pubmed]
  21. Sterol-regulated Degradation of Insig-1 Mediated by the Membrane-bound Ubiquitin Ligase gp78. Lee, J.N., Song, B., Debose-Boyd, R.A., Ye, J. J. Biol. Chem. (2006) [Pubmed]
  22. Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake. Gong, Y., Lee, J.N., Lee, P.C., Goldstein, J.L., Brown, M.S., Ye, J. Cell metabolism. (2006) [Pubmed]
  23. Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles. Adams, C.M., Goldstein, J.L., Brown, M.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  24. Hormonal responses to insulin-induced hypoglycemia in man. Watabe, T., Tanaka, K., Kumagae, M., Itoh, S., Takeda, F., Morio, K., Hasegawa, M., Horiuchi, T., Miyabe, S., Shimizu, N. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  25. Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/2. Nazari, H., Takahashi, A., Harada, N., Mawatari, K., Nakano, M., Kishi, K., Ebina, Y., Nakaya, Y. J. Med. Invest. (2007) [Pubmed]
  26. Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells. Suchanek, M., Radzikowska, A., Thiele, C. Nat. Methods (2005) [Pubmed]
  27. Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step. Lee, J.N., Zhang, X., Feramisco, J.D., Gong, Y., Ye, J. J. Biol. Chem. (2008) [Pubmed]
  28. Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment. Coggins, M., Lindner, J., Rattigan, S., Jahn, L., Fasy, E., Kaul, S., Barrett, E. Diabetes (2001) [Pubmed]
  29. Improvement of insulin secretion but not insulin resistance after short term control of plasma glucose in obese type II diabetics. Hidaka, H., Nagulesparan, M., Klimes, I., Clark, R., Sasaki, H., Aronoff, S.L., Vasquez, B., Rubenstein, A.H., Unger, R.H. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  30. Insulin-induced insulin resistance of lipolysis in human adipocytes in organ culture. Stevens, J., Atkinson, R.L., Pohl, S.L. J. Clin. Endocrinol. Metab. (1980) [Pubmed]
  31. Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis. Imrich, R., Rovensky, J., Zlnay, M., Radikova, Z., Macho, L., Vigas, M., Koska, J. Ann. Rheum. Dis. (2004) [Pubmed]
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