2001, Number 2
<< Back Next >>
Gac Med Mex 2001; 137 (2)
Intracellular Signals Intervening in Glucose Control
Cruz M, Velasco E, Kumate J
Language: Spanish
References: 62
Page: 135-146
PDF size: 180.42 Kb.
ABSTRACT
Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the β chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes.
REFERENCES
Abbas AK, Lichtman AH, Pober JS. Cellular and molecular immunology. 2nd ed. W.B. Saunders Company; 1994.
Lodish H, Berk A, Lawrence SZ, Matsudaira P, Baltimore D, Darnell JE. Molecular cell biology. HW Freeman and Company; 1999.
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell. Garland Publishing;. 1994.
Lewin B. Genes VI. Oxford University Press; 1997.
Nystrom H, Quon J. Insulin signaling: metabolic pathways and mechanisms for specificity. Cell Signal 1999;11:563-574.
Hunter SJ, Garvey WT. Insulin action and insulin resistance: diseases involving defects in insulin receptors signal transduction, and glucose transport effector system. AmJ Med 1998;105:331-345.
Seino S, Seino M, Nishi S, Bell GI. Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci 1989;86:114-8.
Seino S, Seino M, Bell GI. Human insulin-receptor gene. Diabetes 1990;39:129-113.
Cheatham B, Kahn CR. Insulin action and the insulin signaling network. Endocr Rev 1995;16:117-142.
Di Gugillemo GM, Drake PG, Baass PC, Authier F, Posner BI, Bergeron JJM. Insulin receptor internalization and signalling. Mol Cell Biochem 1998;182:59-63.
Wang B, Balba Y, Knutson VP. Insulin-induced in situ phosphorylation of the insulin receptor located in the plasma membrane versus endosomes. Biochem Biophys Res Commun 1996; 227:27-34.
Carpentier JL, Paceaud JP. Molecular and cellular biology of insulin-receptor internalization. Ann NY Acad Sci 1994;733:266-278.
13 Sun XJ, Rothenherg PL, Kahn CR, Backer JM, Araki E, Wilden PA, Cahill DA, Goldstein BJ, White MF. The structure of the insulin receptor substrate IRS-1defines a unique signal transduction protein. Nature 1991;352:73-77.
14 Sun XJ, Pons S, Wang LM, Zhang Y, Yenush L, Burks D, Myers MG Jr, Glasheen E, Copciand NG, Jenkins NA., Pierce JH, White MF. The IRS-2 gene on murine chromosome 8 encodes a unique signalling adapter for insulin and cytokine action. Mol Endocrinol 1997;11:251-262.
15 Myers MG Jr, Zhang Y, Aldaz GAI, Gramer TC, Glasheen ET, Yenush L, Wang LM, Sun XJ, Blenis J, Pierce JH, White MF. YMXM motifs and signalling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites. Mol Cell Biol 1996;16:4147-4155.
He W, Craparo A, Zhu Y, O'Neill TJ, Wang LM, Pierce, JH, Gustafson TA. Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor 1 receptors. J Biol Chem 1996;271:11641-11645.
17 Sawka-Verhelle D, Baron V, Mothe l, Filloux C, White MF, Van Obberghen E. Tyr 624 and Tyr 628 in insulin receptor substrate-2 mediate its association with the insulin receptor. J Biol Chem 1997;272:16414-16420.
18 Sun XJ, Pons S, Asano T, Myers MG. Jr, Glasheen, EM, White MF. The Fyn tyrosine kinase binds IRS-1 and forms a distinct signaling complex during insulin stimulation. J Biol Chem. 1996;271(18):10583-10587.
19 Pawson T. Protein modules and signalling network. Nature 1995;373:573-580.
White MF. The IRS-signaling system: a network of docking proteins that mediate insulin action. Mol Cell Biol 1998; 182:3-1 1.
Burks DJ, Wang J, Towery H, Ishibashi O, Lowe D, Riedel H, White MF. IRS pleckstrin homology domains bind to acidic motifs in proteins. J Biol Chem 1998;273(47):31061-31067.
Farah S, Agazie Y, Ohan N, Ngsee JK, Llu J. A Rho-associated protein kinase, ROKA, binds insulin receptor substrate-1 and modulates insulin signaling. J Biol Chem 1998;273:4740-746.
Bloomgarden ZT. Insulin action and the development of type 2 diabetes. Diabetes Care 2000;23(2):248-252.
Tanti J, Gremeaux T, Van OE, Le MB. Serine/threonine phosphorylation of insulin receptor substrate 1 modulases insulin receptor signaling. J Biol Chem 1994;269: 6051-6057.
Paz K, Hemi R, LeRolth D, Karasik A, Elbananyi E, Kanety H, Ziek Y. A molecular basis for insulin resistance. J Biol Chem 1997;272:9351-9356.
Shepherd PR, Whithers Dj, Siddle K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J 1998;333:471-490.
Dhand R, Hara K, Hiles I, Bax B, Gout l, Panayotou G, Fry MJ, Yonezawa K, Kasuga M, Waterfield MD. Pl 3-kinase: structural and functional analysis of inter-subunit interactions. EMBO J 1994;13:511-521.
Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995;9:726-735.
Alessi D, Cohen P. Mechanism of activation and function of protein kinase B. Curr Opin Genet Dev 1998;8:55-62.
Gzech MP, Corvera S. Signaling mechanisms that regulate glucose transport. J Biol Chem 1999;274(4):1865-1868.
Kimura K, Hattori S, Kbuyma Y, Shizawa Y, Takayanagi J, Nakamura S, Toki S, Matsuda Y, Onodera K, Fukui Y. Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatldylinositol 3-kinase. J Biol Chem 1994;269:18961-18967.
Evans JL, Honer CM, Womelsdorf BE, Kaplan EL, Bell PA. The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. Cell Signal 1995;7:367-376.
Shepherd PR, Khan, BB. Glucose transporters and insulin action. N Engl J Med 1999;22:248-57.
Doege H, Schürmann A, Babrenherg G, Brauers A. Joost HG. GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity. J Biol Chem 2000;275(21):16275-16280.
Kandror KV, Pilch PF. Compartmentalization of protein traffic in insulin-sensitive cells. Am J Physiol. 1996;271:E1-14.
Gould GW, Holman GD. The glucose transporter family: structure, function and tissue-specific expression. Biochem J 1993;295:329-341.
Lamothe B, Baudry A, Desbois P, Lamotte L, Bucchini D, Meyts PD, Joshi RL. Genetic engineering in mice: impact on insulin signalling and action. Biochem J 1998; 335:193-204.
Ebeling P, Koistinen HA, Koivisto VA. Insulin-independent glucose transport regulates insulin sensitivity. FEBS Lett 1998;436:301-303.
Proud CG, Denton RM. Molecular mechanisms for the control of translation by insulin. Biochem J 1998;328:329-341.
Kahn BB, Rossetti L. Type 2 diabetes-Who is conducting the orchestra?. Nat Gen1998;20:223-226.
Kahn CR, Vicent D, Doria A. Genetics of non-insulin-dependent (type II) diabetes mellitus. Annu Rev Med 1996:47:509-531.
Meyts O. The diabetogenes concept of NIDDM. Adv Exp Med Biol 1993;334:89-100.
Laakso M, Malkki M, Kekälänen P, Kuusisto J. Dech 88. Insulin receptor substrate-1 variants in non-insulin-dependent diabetes. J Clin Invest 1994;94:1141-1146.
Carvalho E, Jansson PA, Axelsen M, Eriksson JW, Huang X, Groop L, Rondinone C, Sjöstrom L, Smith U. Low cellular IRS-1 gene and protein expression predict insulin resistance and NIDDM. FASEB J 1999;13:2173-2178.
Porzio O, Federici M, Hribal MT, Lauro D, Accili D, Lauro R, Borbón P, Sesti C. The Gly972 → Arg asnino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic β cells. J Clin Invest 1999;104:357-364.
Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF, Accili D. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest 2000;105:199-205.
Rotamisligil GS, Murray DL, Choy LN, Splegelman BM. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci 1994;91:4854-4858.
Qiao L, Goldberg JL, Russell JC, Sun XJ. Identification of enhanced serine kinase activity in insulin resistance. J Biol Chem 1999;274:10625-10632.
49 Hotamisligil GS, Peraldi P, Budvari A, Ellis RW, White MF, Spiegelman BM. IRS-I-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha and obesity-induced insulin resistance. Science 1996;271:665-668.
Portha B, Serradadas P, Balibe D, Sukuki KI, Goto Y, Giroix MH. β-cell insensitivity to glucose in the GK rat, a spontaneous non obese model for type II diabetes. Diabetes 1991;40:486-49.
Ortiz A, Ziyadeh FN, Nelison EG. Expression of apoptosis-regulatory genes in renal Gottlieb proximal tubular epithelial cell exposed to high ambient glucose and in diabetic kidneys. J Invest Med 1997;45:50-56.
Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, Bonner-Weir S. Role of apoptosis in failure of β-cell mass compensation for insulin resistance and β-cell defects in the male Zucker diabetic fatty rat. Diabetes 1998;47:358-364.
Shimabukuru M, Wang MY, Zhou YT, Newgard CB. Protection against lipoapoptosis of β cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci USA 1998;95:9558-9561.
Araki E, Lipes MA, Patti ME, Bruning JC, Haag B III, Johnson RS, Kahn CR. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 1994;372:186-190.
Tamemoto H, Kadowaki T, Tobe K. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-I. Nature 1994;372:182-186.
Whiters DJ, Gutierrez JS, Towery H. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998; 391:900-904.
Kulkarni RN, Bruning JC, Winnay JN, Psotie C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 1999;96:329-339.
Kerouz N, Horseh D, Pons S, Kahn CR. Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest 1997;100:3164-3172.
Zierath JR, He L, Guma A, Odegoard WE, Klip A, Waliberg-Renriksson H. Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM. Diabetologia 1996;39(10):1180-1189.
Koranyi L, James D, Mueekler M, Permutt MA. Glucose transporter levels in spontaneously obese (db/db) insulin-resistant mice. J Clin Invest 1990;85:962-967.
Tsakiridis T, Vranlc M, Klip A. Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane. J Biol Chem 1994; 269:29934-29942.
Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, Woodgettm JR, Klip A. Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol 1999;19:4008-4018.