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Insulin Action and Insulin Resistance in Noninsulin-Dependent Diabetes Mellitus

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Clinical Research in Diabetes and Obesity

Part of the book series: Contemporary Biomedicine ((CB,volume 15))

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Abstract

Noninsulin-dependent diabetes mellitus (NIDDM) is a complex metabolic disorder of heterogenous etiology (1–5). There is clearly a strong hereditary component to the disease, but the exact genetic abnormalities are likely to differ among different population groups (6–8). In addition, NIDDM is likely to be multigenic, in that more than one discrete gene defect may exist within a given patient to lead esventually to the NIDDM phenotype. Thus, from a genetic point of view, NIDDM is heterogenous and polygenic, making identification of diabetes genes particularly difficult. Numerous biochemical abnormalities have been identified in NIDDM, and the relative contribution of different physiologic or cellular defects differs among different patient groups (6,7). Regardless of the exact pathophysiologic sequence in a particular patient, once full-blown fasting hyperglycemia develops, a characteristic set of metabolic derangements can be identified in the great majority of patients with NIDDM. The major metabolic abnormalities in NIDDM are summarized in Fig. 1, which depicts the final common pathophysiologic state in a typical NIDDM patient (1). It comprises abnormalities in the pancreatic islets, the liver, and the peripheral insulin target tissues.

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References

  1. Olefsky JM. Pathogenesis of non-insulin dependent diabetes (Type II). In: Endocrinology, 2nd ed. DeGroot LJ, Besser GM, Cahill GM, Marshall JC, Nelson DH, Odell WD, Potts JT Jr, Rubenstein AH, Stenberger E, eds. Philadelphia: W.B. Saunders, pp. 1436–1463,1989.

    Google Scholar 

  2. DeFronzo RA. The triumvirate: 13-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 1988; 37: 667–687.

    PubMed  CAS  Google Scholar 

  3. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  4. Efendic S, Luft R, Wajngot A. Aspects of the pathogenesis of Type 2 diabetes. Endocr Rev 1984; 5: 395–410.

    Article  PubMed  CAS  Google Scholar 

  5. Rotter JL, Vadheim CM, Rimoin DL. Genetics of diabetes mellitus. In: Diabetes Mellitus: Theory and Practice. Rifkin H, Porte D, Jr eds. New York: Elsevier, pp. 378–413, 1990.

    Google Scholar 

  6. Olefsky JM. Insulin action and insulin resistance in non-insulin dependent diabetes mellitus. In: Recent Advances in Insulin Action and Its Disorders. Shigeta Y, Kobayashi M, Olefsky JM, eds. Amsterdam: Excerpta Medica, pp. 81–118, 1991.

    Google Scholar 

  7. Caro JF, Dohm GL, Pories WJ, Sinha MK. Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and Type II diabetes. Diabetes Metab Rev 1989; 5: 665–689.

    Article  PubMed  CAS  Google Scholar 

  8. Olefsky JM. Diabetes mellitus. In; Cecil’s Textbook of Medicine, 18th ed., vol. 2. Wyngaarden JB, Smith LH Jr, Bennett JC, Plum F, eds. Philadelphia: W.B. Saunders, pp. 1291–1310, 1991.

    Google Scholar 

  9. Kolterman OG, Gray RS, Griffin J, Burstein P, Insel J, Scarlett JA, Olefsky JM. Receptor and post-receptor defects contribute to the insulin resistance in non-insulin dependent diabetes mellitus. J Clin Invest 1981; 68: 957–969.

    Article  PubMed  CAS  Google Scholar 

  10. Revers RR, Fink R, Griffin J, Olefsky JM, Kolterman OG. Influence of hyperglycemia on insulin’s in vivo effects of Type II diabetes. J Clin Invest 1984; 73: 664–672.

    Article  PubMed  CAS  Google Scholar 

  11. Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in non-diabetic and non-insulindependent diabetic subjects. J Clin Invest 1984; 74: 1238–1246.

    Article  PubMed  CAS  Google Scholar 

  12. Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. New Engl J Med 1992; 327: 707–713.

    Article  PubMed  CAS  Google Scholar 

  13. Ward WK, Beard JC, Halter JB, Pfeifer MA, Porte D Jr. Pathophysiology of insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes Care 1984; 7: 491–502.

    Article  PubMed  CAS  Google Scholar 

  14. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–233.

    PubMed  CAS  Google Scholar 

  15. Nolan JJ, Freidenberg G, Henry R, Reichart D, Olfesky JM. Role of human skeletal muscle insulin receptor kinase in the in vivo insulin resistance of noninsulin dependent diabetes mellitus and obesity. J Clin Endocrinol Metab 1994; 78: 471–477.

    Article  PubMed  CAS  Google Scholar 

  16. Lillioja S, Mott DM, Howard B, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba B, Zurlo F, Swinburn B, Bogardus C. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. New Engl J Med 1988; 318: 1217–1225.

    Article  PubMed  CAS  Google Scholar 

  17. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of Type II diabetes in the offspring of diabetic parents. Ann Int Med 1990; 13: 909–915.

    Google Scholar 

  18. Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH. The natural history of impaired glucose tolerance in the Pima Indians. New Engl J Med 1988; 319: 1500–1505.

    Article  PubMed  CAS  Google Scholar 

  19. Lilioja S, Mott DM, Spraul M, Ferraro R, Foley J, Ravussin E, Knowler W, Bennett PH, Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non-insulindependent diabetes mellitus, prospective studies of Pima Indians. New Engl J Med 1993; 329: 1988–1992.

    Article  Google Scholar 

  20. Rosen OM. After insulin binds. Science 1987; 237: P1452–1458.

    Article  Google Scholar 

  21. Kahn CR, White MF. The insulin receptor and the molecular mechanism of insulin action. J Clin Invest 1988; 82: 1151–1156.

    Article  PubMed  CAS  Google Scholar 

  22. Olefsky JM. The insulin receptor: a multi-functional protein. Diabetes 1990; 39: 1009–1016.

    Article  PubMed  CAS  Google Scholar 

  23. Haring HU. The insulin receptor: signaling mechanism and contribution to the pathogenesis of insulin resistance. Diabetologia 1991; 34: 848–861.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Tomqvist HE, Pierce MW, Frackelton AR. Identification of insulin receptor tyrosine residues autophosphorylated in vitro. J Biol Chem 1987; 262: 10, 212–10, 219.

    Google Scholar 

  26. White MF, Shoelson SE, Keutmann H, Kahn CR. A cascade of tyrosine autophosphorylation of the 13-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem 1988; 263: 2969–2980.

    PubMed  CAS  Google Scholar 

  27. Fink RI, Wallace P, Brechtel G, Olfesky JM. Evidence that glucose transport is rate-limiting for in vivo glucose uptake. Metabolism 1992; 41: 897–902.

    Article  PubMed  CAS  Google Scholar 

  28. Idstrom J-P, Rennie MJ, Schersten T, Bylund-Fellenius A-C. Membrane transport in relation to net uptake of glucose in the perfused rat hindlimb stimulatory effect of insulin hypoxia and contractile activity. Biochem J 1986; 233: 131–137.

    PubMed  CAS  Google Scholar 

  29. Kubo K, Foley JE. Rate-limiting steps for insulin-mediated glucose uptake into perfused rat hindlimb. Am J Physiol 1986; 250: E100–102.

    PubMed  CAS  Google Scholar 

  30. Pessin JE, Bell GI. Mammalian facilitative glucose transport family: structure and molecular regulation. Ann Rev Physiol 1992; 84: 911–930.

    Article  Google Scholar 

  31. Mueckler M. Family of glucose transporter genes. Diabetes 1990; 39: 6–11.

    Article  PubMed  CAS  Google Scholar 

  32. Cushman SW, Wardzala LJ. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. J Cell Biochem 1980; 255: 4758–4762.

    CAS  Google Scholar 

  33. Kono T, Suzuki K, Dansey LE, Robinson FW, Blewis TL. Energy-dependent and protein synthesis-independent recycling of the insulin-sensitive glucose transport mechanism in fat cells. J Biol Chem 1981; 256: 6400–6407.

    PubMed  CAS  Google Scholar 

  34. Kahn BB. Facilitative glucose transporters: regulatory mechanisms and dysregulation in diabetes. J Clin Invest 1992; 89: 1367–1374.

    Article  PubMed  CAS  Google Scholar 

  35. Garvey WT, Maianu JA, Hancock JA, Golichowski AM, Baron A. Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes 1992; 41: 465–475.

    Article  PubMed  CAS  Google Scholar 

  36. Freidenberg GR, Henry RR, Klein HH, Reichart DR, Olfesky JM. Decreased kinase activity of insulin receptors from adipocytes of non-insulin dependent diabetic (NIDDM) subjects. J Clin Invest 1987; 79: 240–250.

    Article  PubMed  CAS  Google Scholar 

  37. Caro JR, Ittoop 0, Pories WJ, Meelheim D, Flickinger EG, Thomas F, Jenquin M, Silverman JF, Khazanie PG, Sinha MK. Studies on the mechanism of insulin resistance in the liver from humans with non-insulin-dependent diabetes. J Clin Invest 1986; 78: 249–258.

    Article  PubMed  CAS  Google Scholar 

  38. Caro JF, Sinha MK, Raju SJ, Ittoop 0, Pories WJ, Flickinger EG, Meelheim D, Dohm GL. Insulin receptor kinase in human skeletal muscle from obese subjects with and without non-insulindependent diabetes. J Clin Invest 1987; 79: 1330–1337.

    Article  PubMed  CAS  Google Scholar 

  39. Amer P, Pollare T, Lithell H, Livingston JN. Defective insulin receptor tyrosine kinase in human skeletal muscle in obesity and Type 2(non-insulin-dependent) diabetes mellitus. Diabetologia 1987; 30: 437–440.

    Article  Google Scholar 

  40. Comi RJ, Grunberger G, Gorden R. Relationship of insulin binding and insulin-stimulated tyrosine kinase activity is altered in Type II diabetes. J Clin Invest 1987; 79: 453–462.

    Article  PubMed  CAS  Google Scholar 

  41. Maegawa H, Shigeta Y, Egawa K, Kobayashi M. Impaired autophosphorylation of insulin receptors from abdominal skeletal muscles in nonobese subjects with NIDDM. Diabetes 1991; 40: 815–819.

    Article  PubMed  CAS  Google Scholar 

  42. Freidenberg GR, Reichart D, Olefsky JM, Henry RR. Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin dependent diabetes mellitus: effects of weight loss. J Clin Invest 1988; 82: 1398–1406.

    Article  PubMed  CAS  Google Scholar 

  43. Kusari J, Verma US, Buse JB, Henry RR, Olefsky JM. Analysis of the gene sequences of the insulin receptor and the insulin sensitive glucose transport (Glut-4) in patients with common type non-insulin dependent diabetes mellitus. J Clin Invest 1991; 88: 1323–1330.

    Article  PubMed  CAS  Google Scholar 

  44. Moller DE, Yokota A, Flier JS. Normal insulin receptor cDNA sequence in Pima Indians with NIDDM. Diabetes 1989; 38: 1496–1500.

    Article  PubMed  CAS  Google Scholar 

  45. Muller HK, Kellerer M, Ermel B, Muhlhofer A, Obermaier-Kusser B, Vogt B, Haring HU. Prevention by protein kinase C inhibitors of glucose-induced insulin receptor tyrosine kinase resistance in rat fat cells. Diabetes 1991; 40: 1440–1448.

    Article  PubMed  CAS  Google Scholar 

  46. Berti L, Mosthaf L, Kroder G, Kellerer M, Tippmer S, Mushack J, Seffer E, Seedorf K, Haring H. Glucose induced translocation of protein kinase C isoforms in rat-1 fibroblases is paralleled by inhibition of the insulin receptor tyrosine kinase. J Biol Chem 1994; 269: 3381–3386.

    PubMed  CAS  Google Scholar 

  47. Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widen E, Schalin C, Groop L. Early metabolic defects in persons at increased risk for non-insulin dependent diabetes mellitus. New Engl J Med 1989; 321: 337–343.

    Article  PubMed  CAS  Google Scholar 

  48. Vaag A, Henriksen JE, Madsbad S, Holm N, Beck-Nielsen H. Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 95: 690–698.

    Article  PubMed  CAS  Google Scholar 

  49. Reaven GM, Sageman WS, Swenson RS. Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency. Diabetologia 1977; 13: 459–462.

    Article  PubMed  CAS  Google Scholar 

  50. Rossetti L, Shulman GI, Sawalich W, DeFronzo RA. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest 1987; 80: 1037–1044.

    Article  PubMed  CAS  Google Scholar 

  51. Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin diabetic rats. J Clin Invest 1987; 79: 1510–1515.

    Article  PubMed  CAS  Google Scholar 

  52. Muller HK, Kellerer M, Ermel B, Muhihofer A, Obermaier-Kusser B, Vogt B, Haring HU. Prevention by protein kinase C inhibitors of glucose-induced insulin-receptor tyrosine kinase resistance in rat fat cells. Diabetes 1991; 40: 1440–1448.

    Article  PubMed  CAS  Google Scholar 

  53. Anderson CM, Olefsky JM. Phorbol ester mediated protein kinase C interaction with wild-type and COOH-terminal truncated insulin receptors. J Biol Chem 1991; 266: 21, 760–21, 764.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  55. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 1991; 266: 4706–4712.

    PubMed  CAS  Google Scholar 

  56. Traxinger RR, Marshall S. Coordinated regulation of glutamine:fructose-6-phosphate amidotransferase activity by insulin, glucose, and glutamine. Role of hexosamine biosynthesis in enzyme regulation. J Biol Chem 1991; 266: 10, 148–10, 154.

    Google Scholar 

  57. Marshall S, Bacote V, Traxinger RR. Complete inhibition of glucose-induced desensitization of the glucose transport system by inhibitors of mRNA synthesis. Evidence for rapid turnover of glutamine:fructose-6-phosphate amidotransferase. J Biol Chem 1991; 266: 10, 155–10, 161.

    Google Scholar 

  58. 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: 1333–1346.

    Article  PubMed  CAS  Google Scholar 

  59. Rossetti L, Hawkins M, Chen W, Gindi J, Barzilai N. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 1995; 96: 132–140.

    Article  PubMed  CAS  Google Scholar 

  60. Baron AD, Zhu J-S, Zhu J-H, Weldon H, Maianu L, Garvey WT. Glucosamine (Glmn) induces insulin resistance (IR) in vivo by affecting glut 4 translocation in skeletal muscle. Implications for glucose toxicity. Diabetes 1995; 44 (Suppl 1): 15A.

    Google Scholar 

  61. Daniels MC, Ciaraldi TP, Henry RR, Nikoulina RR, McClain DA. Glutamine:fructose-6phosphate amido-transferase (GFA) activity in cultured human skeletal muscle cells from control and NIDDM subjects is regulated by glucose. Diabetes 1995; 44 (Suppl 1): 16A.

    Article  Google Scholar 

  62. Wing RR, Blair EH, Bononi P, Marcus MD, Watanabe R, Bergman RN. Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care 1994; 17: 30–36.

    Article  PubMed  CAS  Google Scholar 

  63. Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M. Relative effects of caloric restriction and weight loss in non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993; 77: 1287–1293.

    Article  PubMed  CAS  Google Scholar 

  64. Beck-Nielsen H, Pederson O, Lindskov HO. Normalization of the insulin sensitivity and the cellular insulin binding during treatment of obese diabetics for one year. Acta Endocrinol 1979; 90: 103–112.

    PubMed  CAS  Google Scholar 

  65. Reaven GM, Doberne L, Greenfield MS. Comparison of insulin secretion and in vivo insulin action in nonobese and moderately obese individuals with non-insulin-dependent diabetes mellitus. Diabetes 1982; 31: 382–384.

    Article  PubMed  CAS  Google Scholar 

  66. Hollenbeck CB, Chen YDI, Reaven GM. A comparison of the relative effects of obesity and noninsulin-dependent diabetes mellitus on in vivo insulin-stimulated glucose utilization. Diabetes 1984; 33: 622–626.

    Article  PubMed  CAS  Google Scholar 

  67. Firth R, Bell P, Rizza R. Insulin action in non-insulin-dependent diabetes mellitus: the relationship between hepatic and extrahepatic insulin resistance and obesity. Metabolism 1987; 36: 1091–1095.

    Article  PubMed  CAS  Google Scholar 

  68. Campbell PJ, Carlson MG. Impact of obesity on insulin action in NIDDM. Diabetes 1993; 42: 405–410.

    Article  PubMed  CAS  Google Scholar 

  69. Ludvik B, Nolan JJ, Baloga J, Sacks D, Olefsky J. Effect of obesity on insulin resistance in normal subjects and patients with NIDDM. Diabetes 1995; 44: 1121–1125.

    Article  PubMed  CAS  Google Scholar 

  70. Reynet C, Kahn CR. Rad: a member of the ras family overexpressed in muscle of Type II diabetic humans. Science 1993; 262: 1441–1444.

    Article  PubMed  CAS  Google Scholar 

  71. Zhu J, Reyneet C, Caldwell JS, Kahn CR. Characterization of rad, a new member of ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity. J Biol Chem 1995; 270: 4805–4812.

    Article  PubMed  CAS  Google Scholar 

  72. Patti ME, Vestergaard H, Reynet C, Moyers J, Pedersen O, Kahn CR. Rad expression in human skeletal muscle correlates inversely with insulin-stimulated glucose disposal. J Invest Med 1995; 43 (Suppl 2): 322A.

    Google Scholar 

  73. Moyers JS, Reynet C, Zhu J, Bilan PJ, Kahn CR. A role for rad as an inhibitor of insulin-stimulated glucose transport. Diabetes 1995; 44 (Suppl 1): 302.

    Google Scholar 

  74. Hotamisligil SG, Spiegelman BM. Tumor necrosis factor a: a key component of the obesity-diabetes link. Diabetes 1994; 43: 1271–1278.

    Article  PubMed  CAS  Google Scholar 

  75. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87–91.

    Article  PubMed  CAS  Google Scholar 

  76. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. TNF-a inhibits signaling from insulin receptor. Proc Natl Acad Sci USA 1994; 91: 4854 4858.

    Google Scholar 

  77. Lang CH, Dobrescu C, Bagby GJ. Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 1992; 130: 43–52.

    Article  PubMed  CAS  Google Scholar 

  78. Hotasmisligil GS, Budavari A, Murray DL, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes: central role of tumor necrosis factor-a. J Clin Invest 1994; 94: 1543–1549.

    Article  Google Scholar 

  79. Hotasmisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-a in human obesity and insulin resistance. J Clin Invest 1995;

    Google Scholar 

  80. -2415.

    Google Scholar 

  81. Maddux BA, Sbraccia P, Kumakura S, Hasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven GM, Goldfine ID. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995; 373: 448–451.

    Article  PubMed  CAS  Google Scholar 

  82. Sbraccia P, Goodman PA, Maddux BA, Wong KY, Chen Y-DI, Reaven GM, Goldfine ID. Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patients with insulin resistance and NIDDM. Diabetes 1991; 40: 295–299.

    Article  PubMed  CAS  Google Scholar 

  83. Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW. Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule amino acid sequence, and chromosomal location. J Biol Chem 1990; 265: 17, 506–17, 511.

    Google Scholar 

  84. Ciaraldi TP, Molina JM, Olefsky JM. Insulin action kinetics in adipocytes from obese and noninsulin dependent diabetes mellitus subjects: identification of multiple cellular defects in glucose transport. J Clin Endocrinol Metab 1991; 72: 876–882.

    Article  PubMed  CAS  Google Scholar 

  85. Prager R, Wallace P, Olefsky JM. In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects. J Clin Invest 1986; 78: 472–481.

    Article  PubMed  CAS  Google Scholar 

  86. King GL, Johnson SM. Receptor mediated transport of insulin across endothelial cells. Science 1985; 227: 1583–1586.

    Article  PubMed  CAS  Google Scholar 

  87. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. J Clin Invest 1990; 85: 1844–1852.

    Article  PubMed  CAS  Google Scholar 

  88. Freidenberg GR, Suter S, Henry RR, Nolan J, Reichart D, Olefsky JM. Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle. Diabetes 1994; 43: 118–126.

    Article  PubMed  CAS  Google Scholar 

  89. Karnieli E, Zarnowski MJ, Hissin PJ, Simpson IA, Salans LB, Cushman SW. Insulin stimulated translocation of glucose transport systems in the isolated rat adipose cell: time course, reversal, insulin concentration dependency, and relation to glucose transport activity. J Biol Chem 1981; 256: 4772–4777.

    PubMed  CAS  Google Scholar 

  90. Kono T, Robinson FW, Blevins TL, Ezaki O. Evidence that translocation of the glucose transport activity is the major mechanism of insulin action on glucose transport in fat cells. J Biol Chem 1982; 257: 10, 942–10, 947.

    Google Scholar 

  91. Nolan JJ, Baloga J, Ludvik B. Time course of delayed insulin action in NIDDM. Diabetes 1995; 44: (Suppl 1) 195A.

    Google Scholar 

  92. Yang YJ, Hope ID, Ader M, Bergman RN. Insulin transport across capillaries in rate limiting for insulin action in dogs. J Clin Invest 1989; 84: 1620–1628.

    Article  PubMed  CAS  Google Scholar 

  93. Poulin RA, Steil GM, Moore DM, Ader M, Bergman RN. Dynamics of glucose production and uptake are more closely related to insulin in hindlimb lymph than in thoracic duct lymph. Diabetes 1994; 43: 180–190.

    Article  PubMed  CAS  Google Scholar 

  94. Miles PDG, Levisetti M, Reichart D, Khoursheed M, Moosa AR, Olefsky JM. Kinetics of insulin action in vivo: identification of rate-limiting steps. Diabetes 1995; 44: 947–953.

    Article  PubMed  CAS  Google Scholar 

  95. Castillo C, Bogardus C, Bergman R, Thuillez P, Lillioja S. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men. J Clin Invest 1994; 93: 10–16.

    Article  PubMed  CAS  Google Scholar 

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Nolan, J.J., Olefsky, J.M. (1997). Insulin Action and Insulin Resistance in Noninsulin-Dependent Diabetes Mellitus. In: Draznin, B., Rizza, R. (eds) Clinical Research in Diabetes and Obesity. Contemporary Biomedicine, vol 15. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-3906-0_8

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