Glucose transporters and insulin action: Implications for insulin resistance and diabetes mellitus

New England Journal of Medicine

Volumn 341, Issue 4, 1999, Pages 248-257

  Shepherd, Peter R ^a   Kahn, Barbara B ^b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE TRANSPORTER;

DIABETES MELLITUS; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HUMAN; INSULIN METABOLISM; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

ADIPOCYTES; ANIMALS; BIOLOGICAL TRANSPORT; DIABETES MELLITUS; GLUCOSE; GLUCOSE TRANSPORTER TYPE 4; HEMOSTASIS; HUMANS; INSULIN; INSULIN RESISTANCE; INTRACELLULAR MEMBRANES; MONOSACCHARIDE TRANSPORT PROTEINS; MUSCLE PROTEINS; MUSCLE, SKELETAL; SIGNAL TRANSDUCTION;

EID: 0033595121     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199907223410406     Document Type: Review

References (103)

1. Wright EM, Turk E, Zabel B, Mundlos S, Dyer J. Molecular genetics of intestinal glucose transport. J Clin Invest 1991;88:1435-40.
2. DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997;5:177-269.
3. Fink RI, Wallace P, Brechtel G, Olefeky JM. Evidence that glucose transport is rate-limiting for in vivo glucose uptake. Metabolism 1992;41:897-902.
4. Katz A, Nyomba BL, Bogardus C. No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia. Am J Physiol 1988;255:E942-E945.
5. Yki-Jarvinen H, Young AA, Lamkin C, Foley JE. Kinetics of glucose disposal in whole body and across the forearm in man. J Clin Invest 1987; 79:1713-9.
6. Yki-Jarvinen H, Sahlin K, Ren JM, Koivisto VA. Localization of rate-limiting defect for glucose disposal in skeletal muscle of insulin-resistant type 1 diabetic patients. Diabetes 1990;39:157-67.
7. Rothman DL, Shulman RG, Shulman GI. 31-P nuclear magnetic resonance measurements of muscle glucose-6-phosphate: evidence for reduced insulin-dependent muscle glucose transport or phosphorylation activity in non-insulin-dependent diabetes mellitus. J Clin Invest 1992;89:1069-75.
8. Butler PC, Kryshak EJ, Marsh M, Rizza RA. Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM: evidence for primary defect in glucose transport and/or phosphorylation but not oxidation. Diabetes 1990;39:1373-80.
9. Cline GW, Petersen KF, Krssak M, et al. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med 1999;341:240-6.
10. Beck-Nielsen H, Vaag A, Damsbo P, et al. Insulin resistance in skeletal muscles in patients with NIDDM. Diabetes Care 1992;15:418-29.
11. Rothman DL, Magnusson I, Cline G, et at. Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 1995;92:983-7.
12. Rossetti L, Stenbit AE, Chen W, et al. Peripheral but not hepatic insulin resistance in mice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene. J Clin Invest 1997;100:1831-9.
13. Stenbit AE, Tsao TS, Li J, et al. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 1997;3:1096-101.
14. Kandror KV, Pilch PF. Compartmentalization of protein traffic in insulin-sensitive cells. Am J Physiol 1996;271:E1-E14.
15. Gould GW, Holman GD. The glucose transporter family: structure, function, and tissue-specific expression. Biochem J 1993;295:329-41.
16. Holman GD, Kasuga M. From receptor to transporter: insulin signalling to glucose transport. Diabetologia 1997;40:991-1003.
17. Shepherd PR, Withers DJ, Siddle K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J 1998;333:471-90.
18. Frevert EU, Kahn BB. Differential effects of constitutively active phosphatidylinositol 3-kinase on glucose transport, glycogen synthase activity and DNA synthesis in 3T3-L1 adipocytes. Mol Cell Biol 1997;17:190-8.
19. Katagiri H, Asano T, Ishihara H, et al. Overexpression of the catalytic p110alpha of phosphatidylinositol 3-kinase increases glucose transport activity with translocation of glucose transporters in 3T3-L1 adipocytes. J Biol Chem 1996;271:16987-190.
20. Tanti J, Gremeaux T, Grillo S, et al. Overexpression of a constitutively active form of phosphatidylinositol 3-kinase is sufficient to promote Glut 4 translocation in adipocytes. J Biol Chem 1996;271:25227-32.
21. Carey JO, Azevedo JL, Morris PG, Pories WJ, Dohm GL. Okadaic acid, vanadate, and phenylarsine oxide stimulate 2-deoxyglucose transport in insulin-resistant human skeletal muscle. Diabetes 1995;44:682-8.
22. Alessi DR, James SR, Downes CP, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr Biol 1997;7:261-9.
23. Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ. Protein kinase C isotypes controlled by phosphoinositidc 3-kinase through the protein kinase PDK1. Science 1998;281:2042-5.
24. Kohn AD, Barthel A, Kovacina KS, et al. Construction and characterization of a conditionally active version of the scrine/threonine kinase Akt. J Biol Chem 1998;273:11937-43.
25. Standaert ML, Galloway L, Karnam P, Bandyopadhyay G, Moscat J, Farese RV. Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes: potential role in glucose transport. J Biol Chem 1997;272:30075-82.
26. Kotani K, Ogawa W, Matsumoto M, et al. Requirement of atypical protein kinase C lambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. Mol Cell Biol 1998;18:6971-82.
27. Kitamura T, Ogawa W, Sakaue H, et al. Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. Mol Cell Biol 1998;18: 3708-17.
28. Wang Q, Somwar R, Bilan PJ, et al. Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol 1999; 19:4008-18.
29. Krook A, Roth RA, Jiang XJ, Zierath JR, Wallberg-Henriksson H. Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects. Diabetes 1998;47:1281-6.
30. Rea S, James DE. Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 1997;46:1667-77.
31. Seidner G, Alvarez MG, Yeh JI, et al. GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood brain barrier hexose carrier. Nat Genet 1998;18:188-91.
32. Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat Genet 1997;17:324-6. [Erratum, Nat Genet 1998;18:298.]
33. O'Rahilly S, Krook A, Morgan R, Rees A, Flier JS, Moller DE. Insulin receptor and insulin-responsive glucose transporter (GLUT4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population. Diabetologia 1992;35:486-9.
34. Bjorbaek C, Echwald SM, Hubricht P, et al. Genetic variants in promoters and coding regions of the muscle glycogen synthase and the insulin responsive GLUT4 genes in NIDDM. Diabetes 1994;43:976-83.
35. Buse JB, Yasuda K, Lay TP, et al. Human GLUT4/muscle-fat glucose-transporter gene: characterization and genetic variation. Diabetes 1992;41: 1436-46.
36. Abel ED, Shepherd PR, Kahn BB. Glucose transporters and pathophysiologic states. In: Le Roith D, Taylor SI, Olefsky JM, eds. Diabetes mellitus: a fundamental and clinical text. Philadelphia: Lippmcott-Raven, 1996:530-43.
37. Kahn BB. Facilitative glucose transporters: regulatory mechanisms and dysregulation in diabetes. J Clin Invest 1992;89:1367-74.
38. Liu ML, Olson AL, Moye-Rowley WS, Buse JB, Bell GI, Pessin JE. Expression and regulation of the human GLLT4/muscle-fat facilitative glucose transporter gene in transgenic mice. J Biol Chem 1992;267:11673-6.
39. Ren JM, Marshall BA, Mueckler MM, McCaleb M, Amatruda JM, Shulman GI. Overexprcssion of Glut4 protein in muscle increases basal and insulin-stimulated whole body glucose disposal in conscious mice. J Clin Invest 1995;95:429-32.
40. Leturque A, Loizeau M, Vaulont S, Salminen M, Girard J. Improvement of insulin action in diabetic transgenic mice selectively overexpressing GLUT4 in skeletal muscle. Diabetes 1996;45:23-7.
41. Shepherd PR, Gnudi L, Tozzo E, Yang H, Leach F, Kahn BB. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem 1993;268: 22243-6.
42. Gibbs EM, Stock JL, McCoid SC, et al. Glycemic improvement in diabetic db/db mice by overexpression of the human insulin-regulatable glucose transporter (GLUT4). J Clin Invest 1995;95:1512-8.
43. Tozzo E, Gnudi L, Kahn BB. Amelioration of insulin resistance in streptozotocin diabetic mice by transgenic overexpression of GLUT4 driven by an adipose-specific promoter. Endocrinology 1997;138:1604-11.
44. Goodyear LJ, Kahn BB. Exercise, glucose transport and insulin sensitivity. Annu Rev Med 1998;49:235-61.
45. Zierath JR, He L, Guma A, Wahlstrom EO, Klip A, Wallberg-Henriksson H. Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM. Diabetologia 1996;39:1180-9.
46. Goodyear LJ, Giorgino F, Sherman LA, Carey J, Smith RJ, Dohm GL. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest 1995;95:2195-204.
47. Bjornholm M, Kawano Y, Lehtihet M, Zierath JR. Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation. Diabetes 1997;46:524-7
48. Ahmad F, Azevedo JL, Cortright R, Dohm GL, Goldstein BJ. Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes. J Clin Invest 1997; 100:449-58.
49. Ekhebly M, Payette P, Michaliszyn E, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999;283:1544-8.
50. Condonelli G, Vigliotta G, lavorone C, et al. PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus. EMBO J 1997;17:3858-66.
51. Moyers JS, Bilan PJ, Reynet C, Kahn CR. Overexpression of Rad inhibits glucose uptake in cultured muscle and fat cells. J Biol Chem 1996; 271:23111-6.
52. Reynet C, Kahn CR. Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. Science 1993;262:1441-4.
53. Garvey WT, Maianu L, Kennedy A, et al. Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition. Diabetes 1997;46:444-50.
54. Brichard SM, Henquin JC. The role of vanadium in the management of diabetes. Trends Pharmacol Sci 1995;16:265-70.
55. Storlien LH, Baur LA, Kriketos AD, et al. Dietary fats and insulin action. Diabetoiogia 1996;39:621-31.
56. Boden G. Role of fatty acids in the pathogencsis of insulin resistance and NIDDM. Diabetes 1997;46:3-10.
57. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785-9.
58. Roden M, Price TB, Perseghin G, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996;97:2859-65.
59. Dresner A, Laurent D, Marcucci M, et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999;103:253-9.
60. Zierath JR, Housenecht KL, Gnudi L, Kahn BB. High-fat feeding impairs insulin-stimulated GLUT4 recruitment via an early insulin-signaling defect. Diabetes 1997;46:215-23.
61. Hawkins M, Barzilai N, Liu R, Hu MZ, Chen W, Rossetti L. Role of the glucosamine pathway in fat-induced insulin resistance. J Clin Invest 1997;99:2173-82.
62. Yki-Jarvinen H. Glucose toxicity. Endocr Rev 1992;13:415-31.
63. Zierath JR, Galuska D, Nolte LA, Thorne A, Smedgaard-Kristensen I, Wallberg-Henriksson H. Effects of glycaemia on glucose transport in isolated skeletal muscle from patients with NIDDM: in vitro reversal of muscular insulin resistance. Diabetologia 1994;37:270-7.
64. McClain DA, Crook ED. Hexosamincs and insulin resistance. Diabetes 1996;45:1003-9.
65. Baron AD, Zhu JS, Weldon H, Maianu L, Garvey WT. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle: implications for glucose toxicity. J Clin Invest 1995;96:2792-801.
66. Robinson KA, Sens DA, Buse MG. Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles: study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. Diabetes 1993;42: 1333-46.
67. Hebert LF, Daniels MC, Zhou JX, et al. Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin Invest 1996;98:930-6.
68. Yki-Jarvinen H, Daniels MC, Virkamaki A, Makimattila S, DeFronzo RA, McLain D. Increased glutamifie.fructose-6-phosphate amidotransferase activity in skeletal muscle of patients with NIDDM. Diabetes 1996; 45:302-7.
69. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994;43:1271-8.
70. Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA. The expression of TNF alpha by human muscle: relationship to insulin resistance. J Clin Invest 1996;97:1111-6.
71. Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996;45:881-5.
72. Lund S, Holman GD, Schmitz O, Pedersen O. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl Acad Sci U S A 1995; 92:5817-21.
73. Hayashi T, Hirshman MR, Kurth EJ, Winder WW, Goodyear LJ. Evidence for 5′ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998;47:1369-73.
74. Young ME, Radda GK, Leighton B. Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro. Biochem J 1997; 322:223-8.
75. Kishi K, Muromoto N, Nakaya Y, et al. Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. Diabetes 1998; 47:550-8.
76. Lund S, Flyvbjerg A, Holman GD, Larsen FS, Pedersen O, Schmitz O. Comparative effects of IGF-1 and insulin on the glucose transporter system in rat muscle. Am J Physiol 1994;267:E461-E466.
77. Zierath JR, Bang P, Galuska D, Hall K, Wallberg-Henriksson H. Insulin-like growth factor II stimulates glucose transport in human skeletal muscle. FEBS Lett 1992;307:379-82.
78. Sinha MK, Buchanan C, Raineri-Maldonado C, et al. IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells. Am J Physiol 1990;258:E534-E542.
79. Le Roith D. Insulin-like growth factors. N Engl J Med 1997;336:633-40.
80. Zierath JR, Handberg A, Tally M, Wallberg-Henriksson H. C-peptide stimulates glucose transport in isolated human skeletal muscle independent of insulin receptor and tyrosine kinase activation. Diabetoiogia 1996;39: 306-13.
81. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-32. [Erratum, Nature 1995;374:479.]
82. Berti L, Kellerer M, Capp E, Haring HU. Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: evidence for a P3-kinase mediated effect. Diabetologia 1997;40:606-9.
83. Bray GA, York DA. Clinical review 90: leptin and clinical medicine: a new piece in the puzzle of obesity. J Clin Endocrinol Metab 1997;82: 2771-6. [Erratum, J Clin Endocrinol Metab 1997;82:3878.]
84. Sivitz WI, Walsh SA, Morgan DA, Thomas MJ, Haynes WG. Effects of leptin on insulin sensitivity in normal rats. Endocrinology 1997;138: 3395-401.
85. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 1997;389:374-7.
86. Muller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 1997;272:10585-93.
87. Muoio DM, Dohm GL, Fiedorek FT Jr, Tapscott EB, Coleman RA. Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 1997; 46:1360-3. [Erratum, Diabetes 1997;46:1663.]
88. Ranganathan S, Ciaraldi TP, Henry RR, Mudaliar S, Kern PA. Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells. Endocrinology 1998;139:2509-13.
89. Zierath JR, Frevert EU, Ryder JW, Berggren PO, Kahn BB. Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes. Diabetes 1998;47:1-4.
90. Liu L, Karkanias GB, Morales JC, et al. Intracercbroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem 1998;273: 31160-7.
91. Dukes ID, Philipson LH. K+ channels: generating excitement in pancreatic beta-cells. Diabetes 1996;45:845-53.
92. Muller G, Wied S. The sulfonylurca drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro. Diabetes 1993;42:1852-67.
93. Bailey CJ. Metformin and its role in the management of type-2 diabetes. Curr Opin Endocrinol Metab 1997;4:40-7.
94. Matthaei S, Hamann A, Klein HH, et al. Association of metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes. Diabetes 1991;40:850-7.
95. Fischer Y, Thomas J, Rosen P, Kammermeier H. Action of metformin on glucose transport and glucose transporter GLUT1 and GLUT4 in heart muscle cells from healthy and diabetic rats. Endocrinology 1995;136:412-20.
96. Galuska D, Nolte LA, Zierath JR, Wallberg-Henriksson H. Effect of metformin on insulin-stimulated glucose transport in isolated skeletal muscle obtained from patients with NIDDM. Diabetologia 1994;37;826-32.
97. Hulin B, McCarthy PA, Gibbs EM. The glitazone family of antidiabetic agents. Curr Pharm Des 1996;2:85-102.
98. Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996;45:1661-9.
99. Inzucchi SE, Maggs DG, Spollett GR, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 1998;338:867-72.
100. Hofmann C, Lorenz K, Colca JR. Glucose transport deficiency in diabetic animals is corrected by treatment with the oral antihyperglycemic agent pioglitazone. Endocrinology 1991;129:1915-25.
101. Ciaraldi T, Henry RR. Thiazolidinediones and their effects on glucose transporters. Eur J Endocrinol 1997;137:610-2.
102. Szalkowski D, White-Carrington S, Berger J, Zhang B. Antidiabetic thiazolidinediones block the inhibitory effect of tumor necrosis factor-alpha on differentiation, insulin-stimulated glucose uptake, and gene expression in 3T3-L1 cells. Endocrinology 1995;136:1474-81.
103. Hirshman MF, Fagnant PM, Horton ED, King PA, Horton ES. Pioglitazone treatment for 7 days failed to correct the defect in glucose transport and glucose transporter translocation in obese Zucker rat (fa/fa) skeletal muscle plasma membranes. Biochem Biophys Res Commun 1995;208:835-45.