Abstract
Insulin is one of the best studied hormones. The main actions of insulin are to stimulate the synthesis of glycogen, lipids and proteins, through the modulation of the metabolic pathways implicated in these processes, and the stimulation of cell growth. The physiological effects of insulin include the stimulation of the uptake of glucose, amino acids and ions; the regulation of the state of serine-and threonine-phosphorylation of a variety of proteins and rate-limiting enzymes like glycogen phosphorylase, hormone-sensitive lipase and ATP citrate lyase; and the regulation of the expression of the genes for several regulatory enzymes (review by Denton, 1986). All these effects, whose chronology vary from seconds to hours, are initiated by the interaction of the hormone with the insulin receptor, an integral membrane glycoprotein composed of two α (Mr about 130 kDa) and two ß (95 kDa) subunits. The α subunits bind insulin and are linked by disulphide bonds to each other and to the ß-subunits. Following insulin binding, the ß-subunits are rapidly autophosphorylated predominantly at tyrosine residues. Direct evidence, indicating that insulin action depends on the protein tyrosine kinase activity of the insulin receptor, has been obtained by site-directed mutagenesis of the insulin receptor cDNA as well as with monoclonal antibodies to the insulin receptor kinase domain (review by Rosen, 1987).
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References
Albor A, Camara J, Valverde I, Mato JM, Malaisse WJ (1989) Inhibition of insulin release by a putative insulin-mediator in pancreatic islet cells. Med Sci Res 17: 161–162
Alemany S, Mato JM, Strälfors P (1987) Phospho-dephospho-control by insulin is mimicked by a phospho-oligosaccharide in adipocytes. Nature 330: 77–79
Alvarez JF, Cabello MA, Feliu JE, Mato JM (1987) A phosphooligosaccharide mimics insulin action on glycogen phosphorylase and pyruvate kinase activities in isolated rat hepatocytes. Biochem Biophys Res Commun 147: 765–771
Alvarez JF, Varela I, Ruiz-Albusac JM, Mato JM (1988) Localisation of the insulin-sensitive phosphatidylinositol glycan at the outer surface of the cell membrane. Biochem Biophys Res Commun 152: 1455–1462
Chan BL, Chao MV, Saltiel AR (1989) Nerve growth factor stimulates the hydrolysis of glycosyl-phosphatidylinositol in PC-12 cells: A mechanism of protein kinase C regulation. Proc Natl Acad Sci USA 86: 1756–1760
Cozza EN, Vila MC, Gomez-Sanchez CE, Farese RV (1988) ACTH stimulates turnover of the phosphatidylinositol-glycan. Biochem Biophys Res Commun 157: 585–589
Cross GAM (1987) Eukaryotic protein modification and membrane attachment via phosphatidylinositol Cell 48: 179–180
Denton RM (1986) Early events in insulin actions. In: Greengard P, Robison GA (eds) Advances in Cyclic Nucleotide Research. Raven Press, New York, vol 20, p 293
Farese RV, Nair GP, Stadaert ML, Cooper DR (1988) Epidermal growth factor and insulin-like growth factor-I stimulate the hydrolysis of the insulin-sensitive phosphatidylinositolglycan in BC3H1 myocytes. Biochem Biophys Res Commun 156: 1346–1352
Gaulton G, Kelly KL, Mato JM, Jarett L (1988) Regulation and function of an insulin-sensitive glycosyl-phosphatidylinositol during T lymphocyte activation. Cell 53: 963–970
Gottschalk KW, Jarett L (1988) The insulinomimetic effects of the polar head group of an insulin-sensitive glycophospholipid on pyruvate dehydrogenase in both subcellular and whole cell assays. Arch Biochem Biophys 261: 175–185
Kelly KL, Mato JM, Jarett L (1986) The polar head group of a novel insulin-sensitive glycophospholipid mimics insulin action on phospholipid methyltransferase. FEBS letters 209: 238–242
Kelly KL, Mato JM, Merida I, Jarett L (1987a) Glucose transport and antilipolysis are differentially regulated by the polar head group of an insulin-sensitive glycophospholipid. Proc. Natl. Acad. Sci. USA 84: 6404–6407
Kelly KL, Merida I, Wong EHA, DiCenzo D, Mato JM (1987b) A phospho-oligosaccharide mimics the effect of insulin to inhibit isoproterenol-dependent phosphorylation of phospholipid methyltransferase in isolated adipocytes. J Biol Chem 262: 15282–15290
Larner J, Huang LC, Schwartz CFW, Oswald AS, Shen TY, Kinter M, Tang G, Zeller K (1988) Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphatase contains galactosamine and D-chiroinositol. Biochem Biophys Res Commun 151: 1416–1426
Mato JM, Kelly KL, Abler A, Jarett L (1987a) Identification of a novel insulin-sensitive glycosphospholipid from H35 hepatoma cells. J Biol Chem 262: 2131–2137
Mato JM, Kelly KL, Abler A, Jarett L, Corkey BE, Cashel JA, Zopf D (1987b) Partial structure of an insulin-sensitive glycophospholipid. Biochem Biophys Res Commun 152: 1455–1462
Mato JM (1989) Insulin mediators revisited. Cellular Signalling 1: 143–146
Merida I, Corrales FJ, Clemente R, Ruiz-Albusac JM, Villalba M, Mato JM (1988) Different phosphorylated forms of an insulin-sensitive glycosylphosphatidylinositol from rat hepatocytes. FEBS letters 236: 251–255
Obermaier-Kusser B, Mühlbacher C, Mushack J, Seffer E, Ermel B, Machichao F, Schmidt F, Häring HU (1989) Further evidence for a two-step model of glucose-transport regulation. Inositol phosphate-oligosaccharides regulate glucose carrier activity. Biochem J In press
Romero G, Lutrell L, Rogol A, Zeller K, Hewlett E, Larner J (1988) Phosphatidylinositol-glycan anchors of membrane proteins: Potential precursors of insulin mediators. Science 240: 509–511
Rosen OM (1987) After insulin binds. Science 237: 1452–1458
Saltiel AR (1987) Insulin generates an enzyme modulator from hepatic plasma membranes: Regulation of adenosine 3′,5′monophosphate phosphodiesterase, pyruvate dehydrogenase, and adenylate cyclase. Endocrinology 120: 967–972
Saltiel AR, Sorbara-Cazan LR (1987) Inositol glycans mimics the action of insulin on glucose utilization in rat adipocytes. Biochem Biophys Res Commun 149: 1084–1092
Saltiel AR, Fox JA, Sherline P, Cuatrecasas P (1986) Insulin stimulates the hydrolysis of a novel membrane glycolipid causing the generation of cAMP phosphodiesterase modulators. Science 233: 967–972
Strälfors P (1988) Insulin stimulation of glucose uptake can be mediated by diacylglycerol in adipocytes. Nature 335: 554–556
Varela I, Alvarez JF, Ruiz-Albusac JM, Mato JM (1989) Asymmetric distribution of the phosphatidylinositol-linked phosphooligosaccharide that mimics insulin action in the plasma membrane. Submitted
Villalba M, Kelly KL, Mato JM (1988) Inhibition of cyclic AMP-dependent protein kinase by the polar head group of an insulin-sensitive glycophospholipid. Biochim Biophys Acta 968: 69–76
Villalba M, Alvarez JF, Russell D, Mato JM, Rosen 0 (1989) Hydrolysis of glycosyl-phosphatidylinositol in response to insulin is reduced in cells bearing kinase-deficient insulin receptors. Submitted
Witters LA, Watts TD (1988) An autocrine factor from reuber hepatoma cells that stimulates DNA synthesis and acetyl-CoA carboxylase. J Biol Chem 263: 8027–8036
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© 1990 Springer-Verlag Berlin Heidelberg
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Varela, I. et al. (1990). Role of Glycosyl-Phosphatidylinositols in Insulin Signalling. In: Konijn, T.M., Houslay, M.D., Van Haastert, P.J.M. (eds) Activation and Desensitization of Transducing Pathways. NATO ASI Series, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83618-3_10
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DOI: https://doi.org/10.1007/978-3-642-83618-3_10
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