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Insulin receptor/IRS-1/PI 3-kinase signaling system in corticosteroid-induced insulin resistance

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References

  1. Felig P, Bergman M, Integrated physiology of carbohydrate metabolism. In: Rifkin H, Porte D (eds) Ellenberg and Rifkin's diabetes mellitus, Elsevier, New York; 1990

    Google Scholar 

  2. Kahn CR, White MF, Shoelson SE et al., The insulin receptor and its substrate: molecular determinants of early events in insulin action. (Recent Progress in Hormone Research, Vol 48). Academic Press, London, pp 291–339, 1993

    Google Scholar 

  3. Gammeltoft S, Kahn CR, Hormone signaling via membrane receptors. In: DeGroot LJ, Besser M, Burger HG et al. (eds) Endocrinology, W.B. Saunders, Philadelphia, pp 17–65, 1995

    Google Scholar 

  4. Cheatham B, Kahn CR, Insulin action and the insulin signaling network. Endocrinol Rev 16:117–142, 1995

    Google Scholar 

  5. Freychet P, Roth J, Neville DM Jr, Insulin receptors in the liver: specific binding of [125I] insulin to the plasma membrane and its relation to insulin bioactivity. Proc Natl Acad Sci USA 68:1833–1837, 1971

    PubMed  Google Scholar 

  6. Cuatrecasas P, Affinity chromatography and purification of the insulin receptor of liver cell membranes. Proc Natl Acad Sci USA 69:1277–1281, 1972

    PubMed  Google Scholar 

  7. Massague J, Pilch PF, Czech MP, Electrophoretic resolution of three major insulin receptor structures with unique subunit stoichiometries. Proc Natl Acad Sci USA 77:7137–7141, 1981

    Google Scholar 

  8. Kasuga M, Hedo JA, Yamada KM, Kahn CR, The structure of the insulin receptor and its subunits: evidence for multiple non-reduced forms and a 210K possible proreceptor. J Biol Chem 257:10392–10399, 1982

    PubMed  Google Scholar 

  9. Ullrich A, Bell JR, Chen EY et al., Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313:756–761, 1985

    PubMed  Google Scholar 

  10. Ebina Y, Ellis L, Jarnagin K et al., The human insulin receptor cDNA: the structural basis for hormone activated transmembrane signalling. Cell 40:747–758, 1985

    PubMed  Google Scholar 

  11. Seino S, Seino M, Nishi S, Bell GI, Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci USA 86:114–118, 1989

    PubMed  Google Scholar 

  12. Goldstein BJ, Muller-Wieland D, Kahn CR, Variation in insulin receptor mRNA expression in human and rodent tissues. Mol Endocrinol 1:759–766, 1987

    PubMed  Google Scholar 

  13. Sell SM, Reese D, Ossowski VM, Insulin-inducible changes in insulin receptor mRNA splice variants. J Biol Chem 269:30769–30772, 1994

    PubMed  Google Scholar 

  14. Kellerer M, Sesti G, Seffer E, Ullrich A, Haring HU, Altered pattern of insulin receptor isotypes in skeletal muscle membranes of NIDDM patients. Diabetologia 36:628–632, 1993

    PubMed  Google Scholar 

  15. Norgren S, Zierath J, Galuska D, Wallberg-Henriksson H, Luthman H, Differences in the ratio of RNA encoding two isoforms of the insulin receptor between control and NIDDM patients. The RNA variant without exon 11 predominates in both groups. Diabetes 42:675–681, 1993

    PubMed  Google Scholar 

  16. Benecke H, Flier JS, Moller DE, Alternatively spliced variants of the insulin receptor protein. Expression in normal and diabetic human tissues. J Clin Invest 8966:2066–2070, 1992

    Google Scholar 

  17. Hansen T, Biorbaek C, Vestergaard H, Gronskov K, Bak JF, Pedersen O, Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Meta 77:1500–1505, 1993

    Google Scholar 

  18. De Meyts P, Gu JL, Shymko RM, Kaplan BE, Bell GI, Whittaker J, Identification of a ligand-binding region of the human insulin receptor encoded by the second exon of the gene. Mol Endocrinol 4:409–416, 1990

    PubMed  Google Scholar 

  19. Kasuga M, Karlsson FA, Kahn CR, Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science 215:185–187, 1982

    PubMed  Google Scholar 

  20. White MF, Haring HU, Kasuga M, Kahn CR, Kinetic properties and sites of autophosphorylation in the partially purified insulin receptor from hepatoma cells. J Biol Chem 259:255–264, 1984

    PubMed  Google Scholar 

  21. White MF, Shoelson SE, Keutmann H, Kahn CR, A cascade of tyrosine autophosphorylation in the β-subunit activates the insulin receptor. J Biol Chem 263:2969–2980, 1988

    PubMed  Google Scholar 

  22. Yu KT, Czech MP, Tyrosine phosphorylation of the insulin receptor β subunit activates the receptor-associated tyrosine kinase activity. J Biol Chem 259:5277–5286, 1984

    PubMed  Google Scholar 

  23. Ellis L, Clauser E, Morgan DO, Edery M, Roth RA, Rutter WJ, Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell 45:721–732, 1986

    PubMed  Google Scholar 

  24. Wilden PA, Siddle K, Haring E, Backer JM, White MF, Kahn CR, The role of insulin receptor kinase domain autophosphorylation in receptor-mediated activities. J Biol Chem 267:13719–13727, 1992

    PubMed  Google Scholar 

  25. Kasuga M, Zick Y, Blithe DL, Karlsson FA, Haring HU, Kahn CR, Insulin stimulation of phosphorylation of the β-subunit of the insulin receptor: formation of both phosphoserine and phosphotyrosine. J Biol Chem 257:9891–9894, 1982

    PubMed  Google Scholar 

  26. Takayama S, White MF, Lauris V, Kahn CR, Phorbol esters modulate insulin receptor phosphorylation and insulin action in hepatoma cells. Proc Natl Acad Sci USA 81:7797–7801, 1984

    PubMed  Google Scholar 

  27. Takayama S, White MF, Kahn CR, Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. J Biol Chem 263:3440–3447, 1988

    PubMed  Google Scholar 

  28. Ebina Y, Araki E, Taira M, et al., Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity. Proc Natl Acad Sci USA 84:704–708, 1987

    PubMed  Google Scholar 

  29. Pawson T, Protein modules and signalling networks. Nature 373:573–580, 1995

    PubMed  Google Scholar 

  30. White MF, Maron R, Kahn CR, Insulin rapidly stimulates tyrosine phosphorylation of a Mr 185,000 protein in intact cells. Nature 318:183–186, 1985

    PubMed  Google Scholar 

  31. Sun X, Miralpeix M, Myers MG Jr et al., The expression and function of IRS-1 in insulin signal transmission. J Biol Chem 267:22662–22672, 1992

    PubMed  Google Scholar 

  32. White MF, Livingstone JN, Backer JM et al., Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. Cell 54:651–649, 1988

    PubMed  Google Scholar 

  33. Rothenberg PL, Lane WS, Karasik A, Backer J, White M, Kahn CR, Purification and partial sequence analysis of pp 185, the major cellular substrate of the insulin receptor tyrosine kinase. J Biol Chem 266:8302–8311, 1991

    PubMed  Google Scholar 

  34. Sun X, Rothenberg P, Kahn CR et al., The structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352:73–77, 1991

    PubMed  Google Scholar 

  35. Araki E, Sun X, Haag BL et al., Human skeletal muscle insulin receptor substrate-1: characterization of the cDNA, gene and chromosomal localization. Diabetes 42:1041–1054, 1993

    PubMed  Google Scholar 

  36. White MF, Kahn CR, The insulin signaling system. J Biol Chem 269:1–5, 1994

    PubMed  Google Scholar 

  37. Backer JM, Schroeder GG, Kahn CR et al., Insulin stimulation of phosphatidylinositol 3-kinase activity maps to insulin receptor regions required for endogenous substrate phosphorylation. J Biol Chem 267:1367–1374, 1992

    PubMed  Google Scholar 

  38. Backer JM, Myers MG Jr, Shoelson SE et al., The phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J 11:3469–3479, 1992

    PubMed  Google Scholar 

  39. Folli F, Saad MJA, Backer JM, Kahn CR, Insulin stimulation of phosphatidylinositol 3-kinase activity and association with IRS-1 in liver and muscle of the intact rat. J Biol Chem 267:22171–22177, 1992

    PubMed  Google Scholar 

  40. Hadari YR, Tzahar E, Nadiv O et al., Insulin and insulinomimetic agents induce activation of phosphatidylinositol 3′-kinase upon its association with pp 185 (IRS-1) in intact rat livers. J Biol Chem 268:9156, 1993

    Google Scholar 

  41. Whitman M, Downes CP, Keeler M, Keller T, Cantley L, Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332:644–646, 1988

    PubMed  Google Scholar 

  42. Hiles ID, Otsu M, Volinna S et al., Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. Cell 70:419–429, 1992

    PubMed  Google Scholar 

  43. Herman PK, Emr SD, Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation inSaccharomyces cerevisiae. Mol Cell Biol 12:981–990, 1990

    Google Scholar 

  44. Escobedo JA, Navankasattusas S, Kavanaugh WM, Milfay D, Fried VA, Williams LT, cDNA cloning of a novel 85 kD protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF β-receptor. Cell 65:75–82, 1991

    PubMed  Google Scholar 

  45. Carpenter CL, Cantley LC, Phosphoinositide kinases. Biochemistry 29:11147–11156, 1990

    PubMed  Google Scholar 

  46. Cheatham B, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR, Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp 70 S6 kinase, DNA synthesis and glucose transporter translocation. Mol Cell Biol 14:4902–4911, 1994

    PubMed  Google Scholar 

  47. Okada T, Kawano Y, Sakakibara T, Hazeki O, Ui M, Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. J Biochem 269:3568–3573, 1994

    Google Scholar 

  48. Blenis J, Chung J, Erikson E, Alcorta DA, Erikson RL, Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70-S6 kinase signaling systems are indicated by inhibition of protein synthesis. Cell Growth Diff 2:279–285, 1991

    PubMed  Google Scholar 

  49. Kuhne MR, Pawson T, Lienhard GE, Feng G-S, The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase. Syp. J Biol Chem 268:11479–11481, 1993

    Google Scholar 

  50. Tobe K, Matuoka K, Tamemoto H et al., Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. J Biol Chem 268:11167–11171, 1993

    PubMed  Google Scholar 

  51. Sun X, Crimmins DL, Myers MG Jr, Miralpeix M, White MF, Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. Mol Cell Biol 13:7418–7428, 1993

    PubMed  Google Scholar 

  52. Sun X, Wang LM, Zhang Y et al., The structure and function of 4PS reveals IRS-2: a common interface in insulin and cytokine signaling. Nature 377:173–177, 1995

    PubMed  Google Scholar 

  53. Wang LM, Myers MG Jr, Sun X, Aaronson SA, White MF, Pierce JH, IRS-1: essential for insulin and IL-4-stimulated mitogenesis in hematopoietic cells. Science 261:1591–1594, 1993

    PubMed  Google Scholar 

  54. Patti ME, Sun X, Bruning JC et al., IPS/IRS-2 is the alternative substrate of the insulin receptor in IRS-1 deficient mice. J Biol Chem 270:24670–24673, 1995

    PubMed  Google Scholar 

  55. Folli F, Bonfanti L, Renard E, Kahn CR, Merighi A, Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system. J Neurosci 14:6412–6422, 1994

    PubMed  Google Scholar 

  56. Bergman RN, Finegold DT, Ader M, Assessment of insulin sensitivity in vivo. Endocr Rev 6:45–86, 1985

    PubMed  Google Scholar 

  57. Reynet C, Kahn CR, Rad: a member of theras family overexpressed in muscle of type II diabetic humans. Science 262:1441–1444, 1993

    PubMed  Google Scholar 

  58. Almind K, Biorbaek C, Vestergaard H, Hansen T, Echwald S, Pederson O, Amino acid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 342:828–832, 1993

    PubMed  Google Scholar 

  59. Kahn CR, Causes of insulin resistance. Nature 373:384–385, 1995

    PubMed  Google Scholar 

  60. DeFronzo RA, Hendler R, Simonson DC, Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes 31:795–801, 1982

    PubMed  Google Scholar 

  61. Moller DE, Flier JS, Insulin resistance: mechanisms, syndromes, and implications. N Engl J Med 325:938–948, 1991

    PubMed  Google Scholar 

  62. Mondon CE, Reaven GM, Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension. Metabolism 37:303–305, 1988

    PubMed  Google Scholar 

  63. Cahill GF Jr, Action of adrenal contex steroids on carbohydrate metabolism. In: Christy NP (ed) The human adrenal cortex. Harper and Row, New York, pp 205–238, 1971

    Google Scholar 

  64. Exton JH, Miller TB Jr, Harper SC, Park CR, Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. Am J Physiol 230:163–170, 1976

    PubMed  Google Scholar 

  65. O'Brien RM, Granner DK, PEPCK gene as model of inhibitory effects of insulin on gene expression. Diabetes Care 13:327–339, 1990

    PubMed  Google Scholar 

  66. Olefsky JM, Effect of dexamethasone on insulin binding, glucose transport and glucose oxidation of isolated rat adipocytes. J Clin Invest 56:1499–1508, 1975

    PubMed  Google Scholar 

  67. Baxter J, Forsham P, Tissue effects of glucocorticoids. Am J Med 53:573–577, 1972

    PubMed  Google Scholar 

  68. Rebuffe-Scrive M, Krotkiewski M, Elfverson J, Bjorntorp P, Muscle and adipose tissue morphology and metabolism in Cushing's syndrome. J Clin Endocrinol Metab 67:1122–1128, 1988

    PubMed  Google Scholar 

  69. Caro JF, Amatruda JM, Glucocorticoid-induced insulin resistance. J Clin Invest 69:866–875, 1982

    PubMed  Google Scholar 

  70. Amatruda JM, Livingston JN, Lockwood DH, Cellular mechanisms in selected states of insulin resistance: human obesity, glucocorticoid excess and chronic renal failure. Diabetes Metab Rev 3:293–317, 1985

    Google Scholar 

  71. Saad MJA, Folli F, Kahn JA, Kahn CR, Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. J Clin Invest 92:2065–2072 1993

    PubMed  Google Scholar 

  72. Mordes JP, Rossini AA, Animal models of diabetes mellitus. In: Marble A, Krall LP, Bradley RF, Christlieb HR, Soeldner JS (eds) Joslin's diabetes mellitus. Lea and Febiger, Malvern, pp 110–137, 1985

    Google Scholar 

  73. Saad MJA, Araki E, Miralpeix M, Rothenberg PL, White MF, Kahn CR, Regulation of insulin receptor substrate 1 in liver and muscle of animal models of insulin resistance. J Clin Invest 90:1839–1849, 1992

    PubMed  Google Scholar 

  74. Vicario P, Brady EJ, Slater E, Superstein R, Insulin receptor tyrosine kinase activity is unaltered in ob/ob and db/db mouse skeletal muscle membranes. Life Sci 41:1233–1241, 1987

    PubMed  Google Scholar 

  75. Folli F, Saad JA, Backer JM, Kahn CR, Regulation of phosphatidylinositol 3-kinase activity in liver and muscle of animal models of insulin-resistant and insulin-deficient diabetes mellitus. J Clin Invest 92:1787–1794, 1993

    PubMed  Google Scholar 

  76. Saad MJA, Pimenta WP, Paccola GMGF, Picinato CE, Foss MC, Effect of glucose ingestion on peripheral glucose metabolism in normal man. Diabetes Metab 15:5–10, 1989

    Google Scholar 

  77. Saad MJA, Folli F, Kahn CR, Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in fao hepatoma cells. Endocrinology 136: 1579–1588, 1995

    PubMed  Google Scholar 

  78. Saad MJA, Folli F, Araki E, Hashimoto N, Csermely P, Kahn CR, Regulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in 3R3-F442A adipocytes. Effects of differentiation, insulin and dexamethasone. Mol Endocrinol 8:545–557, 1994

    PubMed  Google Scholar 

  79. Fantus G, Saviolakis GA, Hedo JA, Gorden P, Mechanism of glucocorticoid-induced increase in insulin receptors of cultured human lymphocytes. J Biol Chem 257:8277–8283, 1982

    PubMed  Google Scholar 

  80. Salhanick AI, Krupp MN, Amatruda JM, Dexamethasone stimulates insulin receptor synthesis in cultured rat hepatocytes. J Biol Chem 258:14130–14135, 1983

    PubMed  Google Scholar 

  81. Rice KM, Lienhard GE, Garner CW, Regulation of the expression of pp 160, a putative insulin receptor signal protein, by insulin, dexamethasone, and 1-methyl-3-isobutylxanthine in 3T3-L1 adipocytes. J Biol Chem 267:10163–10167, 1992

    PubMed  Google Scholar 

  82. Savitsky K, Bar-Shira A, Gilad S et al., A single ataxia telangectasia gene with a product similar to PI 3-kinase. Science 268: 1749–1753, 1995

    PubMed  Google Scholar 

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Folli, F., Saad, M.J.A. & Kahn, C.R. Insulin receptor/IRS-1/PI 3-kinase signaling system in corticosteroid-induced insulin resistance. Acta Diabetol 33, 185–192 (1996). https://doi.org/10.1007/BF02048541

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