Acta Diabetologica

, Volume 33, Issue 2, pp 87–99 | Cite as

Insulin resistance in non-insulin-dependent diabetes mellitus

A review
  • A. A. Alzaid


Public Health Diabetes Mellitus Internal Medicine Insulin Resistance Metabolic Disease 
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  1. 1.
    Reaven GM, Pathophysiology of insulin resistance in human disease. Physiol Rev 75:473–486, 1995Google Scholar
  2. 2.
    Olefsky JM, Nolan JJ, Insulin resistance and non-insulin-dependent diabetes: cellular and molecular mechanisms. Am J Clin Nutr 61 [Suppl]:980S–986SGoogle Scholar
  3. 3.
    Beck-Nielsen H, Groop LC, Metabolic and genetic characterization of prediabetic states. J Clin Invest 94:1714–1721, 1994Google Scholar
  4. 4.
    Yki-Jarvinen H, Pathogenesis of non-insulin-dependent diabetes. Lancet 343:91–95, 1994Google Scholar
  5. 5.
    Kahn CR, Insulin action, diabetogenes, and the cause of type 2 diabetes. Diabetes 43:1066–1084, 1994Google Scholar
  6. 6.
    DeFronzo RA, Bonadonna RC, Ferrannini E, Pathogenesis of NIDDM: a balanced overview. Diabetes Care 15:318–368, 1992Google Scholar
  7. 7.
    Himsworth HP, Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1:127–130, 1936Google Scholar
  8. 8.
    Himsworth HP, Kerr RB, Insulin sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci 4:119–152, 1939Google Scholar
  9. 9.
    Yalow RS, Berson SA, Immunoassay of endogenous plasma insulin in man. J Clin Invest 39:1157–1175, 1960Google Scholar
  10. 10.
    Yalow RS, Berson SA, Plasma insulin concentrations in nondiabetic and early diabetic subjects: determinations by a new sensitive immunoassay technique. Diabetes 9:254–260, 1960Google Scholar
  11. 11.
    DeFronzo RA, Tobin JD, Andres R, Glucose clamp technique: a method for qualifying insulin secretion and resistance. Am J Physiol 273:E214–E223, 1979Google Scholar
  12. 12.
    Bergman RN, Ider YZ, Bowden CR, Cobelli C, Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677, 1979Google Scholar
  13. 13.
    Shen SW, Reaven GM, Farquhar JW, Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest 49:2151–2160, 1970Google Scholar
  14. 14.
    Harano Y, Ohgaku S, Hidaka H, Haneda K, Kikkawa R, Shigeta Y, Abe H, Glucose, insulin, and somatostatin infusion for the determination of insulin sensitivity. J Clin Endocrinol Metab 45:1124–1127, 1977Google Scholar
  15. 15.
    Alzaid A, Rizza RA, Insulin resistance and its role in the pathogenesis of NIDDM and glucose intolerance. In: Moller D (ed) Insulin resistance. Wiley, Chichester, pp 143–186, 1993Google Scholar
  16. 16.
    Scheen AJ, Paquot N, Castillo MJ, Lefevre PJ, How to measure insulin action in vivo. Diabetes Metabol Rev 10:151–188, 1994Google Scholar
  17. 17.
    Saad MF, Anderson RL, Laws A, Watanabe RM, Kades WW, Chen Y-DI, Sands RE, Pei D, Savage PJ, Bergman RN, A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across a spectrum of glucose tolerance. Diabetes 43:1114–1121, 1994Google Scholar
  18. 18.
    Hollenbeck C, Reayen GM, Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose balance. J Clin Endocrinol Metab 64:1169–1173, 1987Google Scholar
  19. 19.
    Lindahl B, Asplud K, Hallmans G, High serum insulin, insulin resistance and their associations with cardiovascular factors: the Northern Sweden MONICA population Study. J Intern Med 234:263–270, 1993Google Scholar
  20. 20.
    Zawadski JK, Bogardus C, Foley JE, Insulin action in obese non-insulin dependent diabetes and their isolated adipocytes before and after weight loss. Diabetes 36:227–236, 1982Google Scholar
  21. 21.
    Rosenthal M, Haskel WL, Soloman R, Widstron A, Reaven GM, Demonstration of relationship between level of physical training and insulin-stimulated glucose utilization in normal humans. Diabetes 32:408–411, 1983Google Scholar
  22. 22.
    Shulz B, Ratzman KP, Albrecht G, Diurnal rhythm of insulin sensitivity in subjects with normal and impaired glucose tolerance. Exp Clin Endocrinol 81:262–272, 1983Google Scholar
  23. 23.
    Alzaid AA, Dinneen SF, Moyer TP, Rizza RA, Effects of insulin on plasma magnesium in non-insulin-dependent diabetes mellitus: evidence for insulin resistance. J Clin Endocrinol Metab 80:1376–1381, 1995Google Scholar
  24. 24.
    Paolisso G, Sgambato S, Giugliano D, Torella R, Varricchio M, Scheen AJ, D'Onofrio F, Lefevre PJ, Impaired insulin induced erythrocyte magnesium accumlation is correlated to impaired insulin-mediated glucose disposal in type 2 diabetes patients. Diabetologia 31:910–915, 1988Google Scholar
  25. 25.
    Rossetti L, Giaccari A, DeFronzo RA, Glucose toxicity. Diabetes Care 13:610–630, 1990Google Scholar
  26. 26.
    Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH, The natural history of impaired glucose tolerance in Pima Indians. N Engl J Med 319:1500–1506, 1988Google Scholar
  27. 27.
    Charles MA, Ffonbonne A, Thibult N, Warnet JM, Rosselin GE, Eschwege E, Risk factors for NIDDM in white population: Paris prospective study. Diabetes 40:796–799, 1991Google Scholar
  28. 28.
    Zimmet PZ, Collins VR, Dowse GK, Knight LT, Hyperinsulinaemia in youth is a predictor of type II (non-insulin dependent) diabetes mellitus. Diabetologia 35:536–541, 1992Google Scholar
  29. 29.
    Haffner SM, Stern MP, Mitchell BD, Hazuda HP, Patterson JK, Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity and body fat distribution. Diabetes 39:283–288, 1990Google Scholar
  30. 30.
    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 Intern Med 113:909–915, 1990Google Scholar
  31. 31.
    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. N Engl J Med 321:337–343, 1989Google Scholar
  32. 32.
    Vaag A, Henriksen JE, Beck-Nielsen H, Decreased insulin activation of glycogen synthase in skeletal muscle in young non-obese Caucasian first-degree relatives of patients with non-insulin dependent diabetes mellitus. J Clin Invest 89:782–788, 1992Google Scholar
  33. 33.
    Gulli G, Ferranini E, Stern M, Haffner S, DeFronzo RA, The metabolic profile of NIDDM is fully established in glucose tolerant offspring of two Mexican American NIDDM parents. Diabetes 41:1575–1586, 1992Google Scholar
  34. 34.
    Lillioja S, Mott DM, Howard B, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C, Impaired glucagon tolerance as a disorder of insulin action. N Engl J Med 318:1217–1225, 1988Google Scholar
  35. 35.
    Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C, Insulin resistance and insulin secretory dysfunction as precusors of non-insulin dependent diabetes mellitus. N Engl J Med 329:1988–1992, 1993Google Scholar
  36. 36.
    Bodkin NL, Metzger BL, Hansen BC, Hepatic glucose production and insulin sensitivity preceding diabetes in monkeys. Am J Physiol 256:E676–E681, 1989Google Scholar
  37. 37.
    Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR, Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of 25-year follow up study. Lancet 18:925–929, 1992Google Scholar
  38. 38.
    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 95:690–698, 1995Google Scholar
  39. 39.
    Saad MF, Knowler WC, Pettitt DJ, Nelson RJ, Mott DM, Bennett PH, Sequential changes in serum insulin concentrations during development of non-insulin-dependent diabetes mellitus. Lancet 1:356–359, 1989Google Scholar
  40. 40.
    Swislocki ALM, Donner CC, Frozer E, Chen Y-D I, Reaven GM, Can insulin resistance exist as a primary defect in non-insulin dependent diabetes mellitus? J Clin Endocrinol Metab 64:778–782, 1987Google Scholar
  41. 41.
    Cerasi E, Luft R, Plasma insulin response to glucose infusion in healthy subjects and in subjects with diabetes mellitus. Acta Endocrinol 55:278–304, 1967Google Scholar
  42. 42.
    Temple RC, Carrington CA, Luzio SD, Owens DR, Schneider AE, Sobey WJ, Hales CN, Insulin in non-insulin dependent diabetes. Lancet 1:293–295, 1989Google Scholar
  43. 43.
    Porte D Jr, B-cells in type II diabetes mellitus. Diabetes 40:160–180, 1991Google Scholar
  44. 44.
    Joffe BI, Panz VR, Wing JR, Raal FJ, Seftel HC, Pathogenesis of non-insulin dependent diabetes mellitus in the black population of South Africa. Lancet 340:460–462, 1992Google Scholar
  45. 45.
    Temple RC, Clark P, Schneider A, Nagi DK, Hendra TJ, Yudkin JS, Hales CN, Radioimmunoassay may overestimate insulin in non-insulin dependent diabetes. Clin Endocrinol 32:689–693, 1990Google Scholar
  46. 46.
    Lang DA, Mathiews DR, Burnett M, Turner RC, Brief irregular oscillations of basal plasma insulin and glucose concentrations in diabetic men. Diabetes 30:435–439, 1981Google Scholar
  47. 47.
    O'Rahilly S, Turner RC, Mathiews DR, Impaired pulsatile secretion of insulin in relatives of patients with non-insulin dependent diabetes. N Engl J Med 318:1225–1230, 1988Google Scholar
  48. 48.
    Firth RG, Bell PM, Marsh HM, Hansen I, Rizza RA, Postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus: role of hepatic and extrahepatic tissues. J Clin Invest 77:1525–1532, 1986Google Scholar
  49. 49.
    Polonsky KS, Given BD, Hirsch LJH, Shapiro ET, Beebe C, Frank B, Galloway JA, Van Cauter E, Abnormal patterns of insulin secretion in non-insulin dependent diabetes mellitus. N Engl J Med 318:1231–1239, 1988Google Scholar
  50. 50.
    O'Rahilly SP, Rudenski AS, Burnett MA, Nugent Z, Hosker JP, Darling P, Turner RC, Beta cell dysfunction rather than insulin insensitivity is the primary defect in familial type II diabetes. Lancet 2:360–364, 1986Google Scholar
  51. 51.
    Ward WK, LaCava EC, Paguette TL, Beard JC, Wallum BJ, Porte D Jr. Disproportionate elevation of immunoreactive pro-insulin in type II (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 30:698–702, 1987Google Scholar
  52. 52.
    Yoshioka N, Kuzuya T, Matsuda A, Tanigushi M, Iwamoto Y, Serum proinsulin levels at fasting and after oral glucose load in patients with type II (non-insulin-dependent) diabetes mellitus. Diabetologia 31:355–360, 1988Google Scholar
  53. 53.
    Shiraishi I, Iwamoto Y, Kuzuya T, Matsuda A, Kumakurn S, Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance. Diabetologia 34:737–741, 1991Google Scholar
  54. 54.
    McCance DR, Pettitt DJ, Hanson RL, Jacobsson LTH, Bennett PH, Knowler WC, Glucose, insulin concentrations and obesity in childhood and adolescence as predictors of NIDDM. Diabetologia 37:617–623, 1994Google Scholar
  55. 55.
    Zawalich WS, Kelly GG, The pathogenesis of NIDDM: the role of pancreatic beta cell. Diabetologia 38:986–991, 1995Google Scholar
  56. 56.
    Rizza RA, Mandarino LJ, Baker BA, Gerich JE, Production of insulin resistance by hyperinsulinemia in man. Diabetologia 28:70–75, 1985Google Scholar
  57. 57.
    Service F, Nelson R, Rubenstein A, Go V, Direct effect of insulin on secretion of insulin, glucagon, gastric inhibitory polypeptide and gastrin during maintenance of normoglycemia. J Clin Endocrinol Metab 47:488–493, 1978Google Scholar
  58. 58.
    Cerasi E, Insulin deficiency and insulin resistance in the pathogenesis of NIDDM: is a divorce possible? Diabetologia 38:992–997, 1995Google Scholar
  59. 59.
    Jeanrenaud R, Insulin, corticosterone and the autonomic nervous system in animal obesities: a viewpoint. Diabetologia 38:998–1002, 1995Google Scholar
  60. 60.
    Groop L, Widen E, Ferranini E, Insulin resistance and impaired insulin secretion in the pathogenesis of type 2 diabetes: errors of metabolism or methods? Diabetologia 36:1326–1331, 1993Google Scholar
  61. 61.
    Dinneen S, Gerich J, Rizza R, Carbohydrate metabolism in non-insuln dependent diabetes mellitus. N Engl J Med 327:707–713, 1992Google Scholar
  62. 62.
    Cahill G, Starvation in man. N Engl J Med 282:668–675, 1970Google Scholar
  63. 63.
    Rizza RA, Mandarino LJ, Gerich JE, Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol 240:E630–E639, 1981Google Scholar
  64. 64.
    DeFronzo RA, The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687, 1988Google Scholar
  65. 65.
    Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D, Relationship between insulin secretion, insulin action, and fasting plasma glucose concentration in non-diabetic and non-insulin dependent diabetic subjects. J Clin Invest 74:1238–1246, 1984Google Scholar
  66. 66.
    Consoli A, Nurjhan N, Reilly JJ Jr, Brier DM, Gericer JE, Mechanism of increased gluconeogenesis in non-insulin dependent diabetes mellitus: role of alterations in systemic, hepatic and muscle lactate and alanine metabolism. J Clin Invest 86:2034–2045, 1990Google Scholar
  67. 67.
    Butler PC, Rizza RA, Contribution to postprandial hyperglycaemia and effect on initial splanchnic glucose clearance of hepatic glucose cycling in glucose intolerant or NIDDM patients. Diabetes 40:73–81, 1991Google Scholar
  68. 68.
    Gerich JE, Is muscle the major site of insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus? Diabetologia 34:607–610, 1991Google Scholar
  69. 69.
    DeFronzo RA, Pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: a balanced overview. Diabetologia 35:389–397, 1992Google Scholar
  70. 70.
    Kolterman OG, Gray RS, Griffin J, Burnstein P, Insel T, Scarlett JA, Olefsky JM, Receptor and post-receptor defects contribute to the insulin resistance in non-insulin dependent diabetes mellitus. J Clin Invest 68:957–969, 1981Google Scholar
  71. 71.
    Cavallo-Perin P, Cassade M, Bozzo C, Nuccio P, Dall'omo AM, Marucci, Pagano G, Mechanism of insulin resistance in human liver cirrhosis. J Clin Invest 75:1659–1665, 1985Google Scholar
  72. 72.
    Peires AN, Mueller RA, Struve MF, Smith GA, Kissebah AH, Relationship of androgenic activity to splanchnic insulin metabolism and peripheral glucose utilization in premenopausal women. J Clin Endocrinol Metab 64:162–169, 1987Google Scholar
  73. 73.
    Mitrakou A, Kelly D, Mokan M, Veneman T, Pangburn T, Reilly J, Gerich J, Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med 326:22–29, 1992Google Scholar
  74. 74.
    Butler PC, Kryshak EJ, Marsh M, Rizza RA, Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM. Diabetes 39:1373–1380, 1990Google Scholar
  75. 75.
    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 36:1091–1095, 1987Google Scholar
  76. 76.
    Sacca L, Orofino G, Petrone A, Vigorito C, Differential roles of splanchnic and peripheral tissues in the pathogenesis of impaired glucose tolerance. J Clin Invest 73:1683–1687, 1984Google Scholar
  77. 77.
    Firth RG, Bell PM, Rizza RA, Effects of tolazamide and exogenous insulin action in patients with non-insulin dependent diabetes mellitus. N Engl J Med 314:1280–1286, 1986Google Scholar
  78. 78.
    DeFronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J, Effects of insulin on peripheral and splanchnic glucose metabolism in non-insulin dependent diabetes Mellitus. J Clin Invest 76:149–155, 1985Google Scholar
  79. 79.
    Butterfield WJH, Whichelow MJ, Peripheral glucose metabolism in control subjects and diabetic patients during glucose, glucose-insulin, and insulin sensitivity tests. Diabetologia 1:43–53, 1965Google Scholar
  80. 80.
    Jackson RA, Perry G, Rogers J, Advoni U, Pilkinton TRE, Relationship between the basal glucose concentration, glucose tolerance, and forearm uptake in maturity onset diabetes. Diabetes 22:751–761, 1973Google Scholar
  81. 81.
    Capaldo B, Napoli R, DiBonito P, Albans G, Sacca L, Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin treated type II diabetic patients. J Clin Endocrinol Metab 71:1220–1223, 1990Google Scholar
  82. 82.
    Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG, Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322:223–228, 1989Google Scholar
  83. 83.
    Turk D, Alzaid A, Dinneen S, Nair KS, Rizza R, The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues. J Clin Invest 95:755–762, 1995Google Scholar
  84. 84.
    Alzaid AA, Dinneen SF, Turk DJ, Caumo A, Cobelli C, Rizza A, Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans. J Clin Invest 94:2341–2348, 1994Google Scholar
  85. 85.
    McMahon M, Marsh M, Rizza R, Effects of basal insulin supplementation on the disposition of a mixed meal in obese patients with non-insulin dependent diabetes mellitus. Diabetes 38:291–303, 1989Google Scholar
  86. 86.
    Chiasson JL, Atkinson R, Cherrington A, Keller U, Sinclair-Smith B, Lacy W, Liljenquist J, Effects of insulin at two dose levels on gluconeogenesis from alanine in fasting man. Metabolism 29:810–818, 1980Google Scholar
  87. 87.
    Brosman JT, Pathways of carbon flux in gluconeogenesis. Fed Proc 41:91–95, 1982Google Scholar
  88. 88.
    Ahlorg G, Hagenfeldt L, Wahren J, Influence of lactate infusion or glucose and FFA metabolism in man. Scand J Clin Lab Invest 36:193–201, 1976Google Scholar
  89. 89.
    Dietze G, Wicklmayer M, Hepp K, Bogner W, Mehnert H, Czempiel H, Henftling H, On gluconeogenesis of human liver: accelerated hepatic glucose formation by increased precursor supply. Diabetologia 12:555–561, 1976Google Scholar
  90. 90.
    Jahoor F, Peters E, Wolfe R, The relationship between gluconeogenic substrate and glucose production in humans. Am J Physiol 258:E288–E296, 1990Google Scholar
  91. 91.
    Jensen T, Nurjhan N, Consoli A, Gerich J, Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans: demonstrations of hepatic autoregulation without a change in plasma glucose concentration. J Clin Invest 86:489–497, 1990Google Scholar
  92. 92.
    Puhakainen I, Yki-Jarvinen H, Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM. Diabetes 42:1694–1699, 1993Google Scholar
  93. 93.
    Clore JN, Glickman PS, Nestler JE, Blackard WG, In vivo evidence for hepatic autoregulation during FFA-stimulated gluconcogenesis in normal humans. Am J Physiol 261:E425–429, 1991Google Scholar
  94. 94.
    Moller DE, Flier JS, Insulin resistance: mechanisms, syndromes and implications. N Engl J Med 325:938–948, 1991Google Scholar
  95. 95.
    Rosen OM, After insulin binds. Science 237:1452–1458, 1987Google Scholar
  96. 96.
    Kahn CR, White MF, The insulin receptor and the molecular mechanism of insulin action. J Clin Invest 82:1151–1156, 1988Google Scholar
  97. 97.
    Olefsky JM, The insulin receptor: a multi-functional protein. Diabetes 39:1009–1016, 1990Google Scholar
  98. 98.
    White MF, Maron R, Kahn CR, Insulin rapidly stimulates tyrosine phosphorylation of a M 185,000 protein in intact cells. Nature 318:183–186, 1985Google Scholar
  99. 99.
    Kryshak E, Butler PC, Marsh C, Miller A, Barr D, Polonsky K, Perkins J, Rizza R, Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery. Diabetes 39:142–148, 1990Google Scholar
  100. 100.
    Robinson TJ, Archer JA, Gambhir KK, Hollis VW, Carter L, Bradley C, Erythrocytes: a new type for the evaluation of insulin receptor defects in diabetic humans. Science 205: 200–202, 1979Google Scholar
  101. 101.
    DiPirro R, Fusco A, Lauro R, Testa I, Ferreti F, DeMartins C, Erythrocyte insulin receptors in non-insulin dependent diabetes mellitus. Diabetes 29:96–99, 1980Google Scholar
  102. 102.
    Ward GM, Naylor BA, Sargent RM, Turner RC, Abnormal dietary regulation erythrocyte insulin receptor affinity in non-insulin dependent diabetes mellitus. Clin Endocrinol 20: 671–681, 1984Google Scholar
  103. 103.
    Olefsky JM, Reaven GM, Insulin binding in diabetes relationships with plasma insulin levels and insulin sensitivity. Diabetes 26:680–688, 1977Google Scholar
  104. 104.
    Benzi L, Trischitta V, Ciccarone A, Ceccheti P, Brunetti A, Squatrito S, Marchetti P, Vigneri R, Navalesi R, Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients. Diabetes 39:844–849, 1990Google Scholar
  105. 105.
    Howard B, Hidaka H, Ishibashi F, Fields R, Bennett P, Type II diabetes and insulin resistance: evidence for lack of inherent cellular defects in insulin sensitivity. Diabetes 36:620–625, 1981Google Scholar
  106. 106.
    Well AM, Sutcliff IC, Johnson AB, Taylor R, Abnormal activation of glycogen synthesis in fibroblasts from subjects with NIDDM: evidence for an abnormality specific to glucose metabolism. Diabetes 42:583–589, 1993Google Scholar
  107. 107.
    Taylor SI, Cama A, Accili D, Barbetti F, Quon MJ, Luz Sierra M, Suzuki Y, Koller E, Levy-Toledano R, Wertheimer E, Moncada VY, Katowaki H, Kadowaki T, Mutations in the insulin receptor gene. Endocrinol Rev 3:566–595, 1992Google Scholar
  108. 108.
    Friedenberg GR, Henry RR, Klein HH, Reichart DR, Olefsky JM, Decreased kinase activity in insulin receptors from adipocytes of non-insulin-dependent (NIDDM) subjects. J Clin Invest 79:240–250, 1987Google Scholar
  109. 109.
    Caro J, Sinha M, Raju S, Ittoop O, Pories W, Flickinger E, Meelheim D, Dohm L, Insulin receptor kinase in human skeletal muscle from obese subjects with and without non-insulin dependent diabetes. J Clin Invest 79:1330–1337, 1987Google Scholar
  110. 110.
    Maegawa H, Shigeta Y, Egawa K, Kobayashi M, Impaired autophosphorylation of insulin receptors from abdominal skeletal muscles in non-obese subjects with NIDDM. Diabetes 40:815–819, 1991Google Scholar
  111. 111.
    Caro J, Ittoop O, Pories W, Mcelheim D, Flickinger E, Thomas F, Jenquin M, Khazanie P, Sinha M, Studies on the mechanism of insulin resistance in the liver from humans with non-insulin dependent diabetes. J Clin Invest 78:249–258, 1986Google Scholar
  112. 112.
    Arner P, Einarsson K, Enerth S, Livingston J, Studies of the human liver insulin receptor in non-insulin dependent diabetes mellitus. J Clin Invest 255:E942–E945, 1986Google Scholar
  113. 113.
    Nolan JJ, Freidenberg G, Henry R, Reichart D, Olefsky JM, Role of human skeletal muscle insulin receptor kinase in the in vivo insulin resistance of non-insulin dependent diabetes melitus and obesity. J Clin Endocrinol Metab 78:471–478, 1994Google Scholar
  114. 114.
    Friedenberg 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 82:1398–1406, 1988Google Scholar
  115. 115.
    Maddux BA, Sbraccia P, Kumakura S, Sasson 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 373:448–451, 1995Google Scholar
  116. 116.
    Kahn CR, Causes of insulin resistance. Nature 373:384–385, 1995Google Scholar
  117. 117.
    Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald SM, Pederson O, Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 342:828–832, 1993Google Scholar
  118. 118.
    Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, Terauchi Y, Ueki K, Kaburagi Y, Satoh S, Sekihara H, Yoshioka S, Horikoshi H, Furuta Y, Ikawa Y, Kasuga M, Yazaki Y, Alzawa S, Insulin resistance and growth retardation in mice lacking receptor substrate-1. Nature 372:181–186 1994Google Scholar
  119. 119.
    Araki E, Lipes MA, Patti M-E, Bruning JC, Haag B, Johnson R, Kahn CR, Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372: 186–189, 1994Google Scholar
  120. 120.
    Clausen JO, Hansen T, Bjorbaek, Ecwald SM, Urhammer SA, Rasmussen S, Andersen CB, Hansen L, Almind K, Winther K, Haraldsdottir, Borch-Johnsen K, Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1. Lancet 346:397–402, 1995Google Scholar
  121. 121.
    Kahn B, Facilitative glucose transporters: regulatory mechanisms and dysregulation in diabetes. J Clin Invest 89:1367–1374 1992Google Scholar
  122. 122.
    Charron MJ, Brosius FC, Alper SL, Lodish HF, A glucose transport protein expressed predominantly in insulin responsive tissues. Proc Natl Acad Sci USA 86:2535–2539, 1989Google Scholar
  123. 123.
    Fukumoto H, Kayano T, Buse JB, Edwards Y, Pilch PF, Bell GI, Seino S, Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J Biol Chem 264:7776–7779, 1989Google Scholar
  124. 124.
    Birnbaum MJ, Identification of a novel gene encoding an insulin-responsive glucose transport protein. Cell 57:305–315 1989Google Scholar
  125. 125.
    James DE, Strube M, Mueckler M, Molecular cloning and characterization of an insulin regulatable glucose transporter. Nature 338:83–87, 1989Google Scholar
  126. 126.
    Kaestner KH, Kristy RJ, McLenihan JC, Braiterman LT, Cornelius P, Pekala PH, Lane MD, Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes. Proc Natl Acad Sci USA 86:3150–3154, 1989Google Scholar
  127. 127.
    Groop L, Bonndonna R, Delprato S, Ratheiser K, Zyck K, Ferrannini E, DeFronzo R, Glucose and free fatty acid metabolism in non-insulin dependent diabetes mellitus: evidence for multiple sites of insulin resistance. J Clin Invest 84:205–213, 1989Google Scholar
  128. 128.
    Golay A, DeFronzo R, Ferrannini E, Simonson D, Thorin D, Acheson K, Thiebaud D, Curchod B, Jequier E, Felber J, Oxidative and non-oxidative metabolism in non-obese type II (non-insulin dependent) diabetic patients. Diabetologia 31: 585–591, 1988Google Scholar
  129. 129.
    Thorburn AW, Gumbiner B, Bulacan F, Wallace P, Henry RP, Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake. J Clin Invest 85:522–529, 1990Google Scholar
  130. 130.
    Kelley DE, Mokan M, Mandarino LJ, Intracellular defects in glucose metabolism in obese patients with NIDDM. Diabetes 41:698–706, 1992Google Scholar
  131. 131.
    Damsbo P, Vaag A, Hother-Nielson O, Beck-Nielsen H, Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin dependent) diabetes mellitus. Diabetologia 34:239–245, 1991Google Scholar
  132. 132.
    Schalin-Jantti C, Harkonen M, Groop LC, Impaired activation of glycogen synthase in people at increased risk for developing NIDDM. diabetes: 598–604, 1992Google Scholar
  133. 133.
    Thiebaud D, DeFronzo RA, Jacot E, Golay A, Acheson K, Maeder E, Jequier E, Felber JP, Effect of long chain triglyceride infusion on glucose metabolism in man. Metabolism 31:1128–1136, 1982Google Scholar
  134. 134.
    Boden G, Ray TK, Smith RH, Owen OE, Carbohydrate oxidation and storage in obese non-insulin dependent diabetic patients. Diabetes 32:982–987, 1983Google Scholar
  135. 135.
    Chiasson JL, Germain L, Srivastava AK, Dupius P, Hormonal regulation of glucose transport in contracting skeletal muscle from normal and diabetic rats. Metabolism 33:617–620, 1984Google Scholar
  136. 136.
    Katz A, Nyomba BL, Bogardus C, No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia Am J Physiol 255:E942–E945, 1988Google Scholar
  137. 137.
    Farrace S, Rossetti L, Hyperglycemia markedly enhances skeletal muscle glycogen synthase activity in diabetic but not in normal conscious rats. Diabetes 41:1453–1463, 1992Google Scholar
  138. 138.
    Gottesman I, Mandarino L, Verdonk C, Rizza R, Gerich, Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man: evidence that insulin increases glucose uptake merely by providing additional transport sites. J Clin Invest 70:1310–1314, 1982Google Scholar
  139. 139.
    Fink RI, Wallace P, Olefsky JM, Effects of aging on glucose-mediated glucose disposal and transport. J Clin Invest 77: 2034–2041, 1986Google Scholar
  140. 140.
    Baron AD, Laakso M, Brechtel G, Edelman SV, Reduced capacity and affinity of skeletal muscle for insulin-mediated glucose uptake in noninsulin-dependent diabetic subjects. J Clin Invest 87:1186–1194, 1991Google Scholar
  141. 141.
    Johnson AB, Argyraki M, Thow JC, Cooper BG, Fulcher G, Taylor R, Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man. Clin Sci 82:219–226, 1992Google Scholar
  142. 142.
    Mansell PI, MacDonald IA, The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans. Metabolism 39:502–510, 1990Google Scholar
  143. 143.
    Garvey WT, Kolterman OG, Correlations between in vivo and in vitro actions of insulin in obesity and diabetes. Diabetes Metab Rev 4:543–570, 1988Google Scholar
  144. 144.
    Henry RR, Wallace P, Olefsky JM, Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin dependent diabetes mellitus. Diabetes 35:990–998, 1986Google Scholar
  145. 145.
    Friedman JE, Dohm JL, Legget-Frasier N, Elton CW, Tapscott EB, Pories WP, Caro JF, Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss: effect on muscle glucose transport and glucose transporter GLUT4. J Clin Invest 89:701–705, 1992Google Scholar
  146. 146.
    Rothman DL, Shulman RG, Shulman GI, 31P 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 89:1069–1075, 1992Google Scholar
  147. 147.
    Garvey WT, Maianu L, Huecksteadt TP, Birnbaum MJ, Molina JM, Ciaraldi TP, Pretranslation suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity. J Clin Invest 87:1072–1081, 1991Google Scholar
  148. 148.
    Sinha MK, Raineri-Maldonado C, Buchanan C, Pories WJ, Carter-Su C, Pilch PF, Caro JF, Adipose tissue glucose transporters in NIDDM: decreased levels of muscle/fat isoform. Diabetes 40:472–477, 1991Google Scholar
  149. 149.
    Garvey W, Huecksteadt T, Mattlaei S, Olefsky J, Role of glucose transporters in the cellular insulin resistance of type II non-insulin dependent diabetes mellitus. J Clin Invest 81: 1528–1536, 1988Google Scholar
  150. 150.
    Handberg A, Vaag A, Damsbo P, Beck-Nielsen H, Vinten J, Expression of insulin regulatable glucose transporters in skeletal muscle from type 2 (non-insulin-dependent) diabetic patients. Diabetologia 33:625–627, 1990Google Scholar
  151. 151.
    Pedersen O, Bak JF, Anderson PH, Lund S, Moller DE, Flier JS, Kahn BB, Evidence against altered expression of GLUTI or GLUTA 4 in skeletal muscle of patients with obesity or NIDDM. Diabetes 39:865–870, 1990Google Scholar
  152. 152.
    Ericksson J, Koranyi L, Bourey R, Schalin-Jantti C, Widen E, Mueckler M, Permutt AM, Groop LC, Insulin resistance in type 2 (non-insulin-dependent) diabetic patients and their release is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle. Diabetologia 35:143–147, 1992Google Scholar
  153. 153.
    Katz EB, Stenbit AE, Hatton K, DePinho R, Charron MJ, Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377:151–155, 1995Google Scholar
  154. 154.
    McGarry JD, What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258:766–770, 1992Google Scholar
  155. 155.
    Randle P, Hales C, Garland P, Newsholme E, The glucose fatty acid cycle: its role in insulin, sensitivity, and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789, 1963Google Scholar
  156. 156.
    Boden G, Jadali F, Effects of lipid on basal carbohydrate metabolism in normal man. Diabetes 40:686–692, 1991Google Scholar
  157. 157.
    Clore JN, Clickman PS, Helm ST, Nestler JE, Blackard SA, Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic man. Diabetes 40:1033–1040, 1991Google Scholar
  158. 158.
    Piatti PM, Monti LD, Pacchioni M, Pontiroli AE, Pozza G, Forearm and insulin mediated glucose uptake and muscle metabolism in man: role of free fatty acids and blood glucose levels. Metabolism 40:926–933, 1991Google Scholar
  159. 159.
    Kleiber H, Munger R, Jallut D, Tappy L, Feily C, Golay A, Frascavola P, Jequier E, Felber JP, Interaction of lipid and carbohydrate metabolism after infusions of lipids or lowering agents: lack of direct relationship between free fatty acid concentration and glucose disposal. Diabete Metab 18:84–90, 1992Google Scholar
  160. 160.
    Ferrannini E, Barrett EJ, Bevilacqua S, DeFronzo RA, Effect of fatty acids on glucose production and utilization in man. J Clin Invest 72:1737–1747, 1983Google Scholar
  161. 161.
    Nuutila P, Koivisto VA, Knuuti J, Ruotsalainen U, Teras M, Haaparanta M, Bergman J, Bioplo-Pulkki L-M, Solin O, Yki-Jarvinen H, Wegelius U, Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo. J Clin Invest 89:1767–1774, 1992Google Scholar
  162. 162.
    Bevilacqua S, Buzzigoli G, Bonadonna R, Brandi LS, Oleggini M, Boni C, Geloni M, Ferrannini E, Operation of Randle's cycle in patients with NIDDM. Diabetes 39:383–389, 1990Google Scholar
  163. 163.
    Eriksson J, Saloranta C, Widen E, Eckstrand A, Franssila-Kallunki A, Schalin C, Groop L, Non-esterified fatty acids do not contribute to insulin resistance in persons at increased risk of developing type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34:192–197, 1991Google Scholar
  164. 164.
    Capaldo B, Napoli R, DiBonito P, Albano G, Sacca L, Dual mechanism of insulin action on human skeletal muscle: identification of an indirect component not mediated by FFA. Am J Physiol 260:E289–E294, 1990Google Scholar
  165. 165.
    Felber J, Ferrannini E, Golay A, Meyer HU, Thiebaud D, Curchod A, Maeder E, Jequier E, DeFronzo RA, Role of lipid oxidation pathogenesis of insulin resistance of obesity and type II diabetes. Diabetes 36:1341–1350, 1987Google Scholar
  166. 166.
    Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen MR, Groop L, Modulation of hepatic glucose production by nonesterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34:409–415, 1991Google Scholar
  167. 167.
    Zhou Y-P, Grill VE, Longterm exposure in rat pancreatic islets to fatty acids inhibits glucose induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93:870–876, 1994Google Scholar
  168. 168.
    Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E, A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38:1213–1217, 1995Google Scholar
  169. 169.
    Reaven GM, The fourth Musketeer — from Alexandre Dumas to Claude Bernard. Diabctologia 38:3–13, 1995Google Scholar
  170. 170.
    Howard BV, Savage PJ, Nagulesparan M, Bennion LJ, Unger RG, Bennett PH, Evidence for marked sensitivity to the antilipolytic action of insulin in obese maturity-onset diabetics. Metabolism 28:744–750, 1979Google Scholar
  171. 171.
    Yki-Jarvinen H, Kubo K, Zawadzki J, Lillioja S, Young A, Abbott W, Foley J, Dissociation of in vitro sensitivities of glucose transport and anti-lipolysis to insulin in NIDDM. Am J Physiol 253:E300–E304, 1987Google Scholar
  172. 172.
    Foley JE, Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes. Diabetes Care 15:773–781, 1992Google Scholar
  173. 173.
    The physican's guide to type II diabete (NIDDM). Diagnosis and treatment. American Diabetes Association, 1984Google Scholar
  174. 174.
    Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims AH, Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin dependent diabetes mellitus. Diabetes 33:311–318, 177Google Scholar
  175. 175.
    Bak JF, Schmitz O, Sorensen NS, Pedersen O, Postreceptor effects of sulphonylurea on skeletal muscle glycogen synthase activity in type II diabetic patients. Diabetes 38:1343–1350, 1989Google Scholar
  176. 176.
    Simonson D, Ferrannini E, Bevilacqua S, Smith D, Barrett E, Carlson R, Defronzo R, Mechanism of improvement in glucose metabolism after chronic glyburide therapy. Diabetes 33:838–845, 1984Google Scholar
  177. 177.
    Kolterman O, Gray R, Shapiro G, Scarlett J, Griffin J, Olefsky J, The acute and chronic effects of sulfonylurea therapy in type II diabetic subjects. Diabetes 33:346–354, 1984Google Scholar
  178. 178.
    Best JD, Judzewitsch RG, Pfeifer MA, Beard JC, Halter JB, Porte D Jr, The effect of chronic sulphonylurea therapy on hepatic glucose production in non-insulin-dependent diabetes. Diabetes 31:333–338, 1982Google Scholar
  179. 179.
    Nosadini R, Avogaro A, Trevisan R, Valenio AM, Tessari P, Duner E, Tiengo A, Velussi M, Del Prato S, Kruetzenberg S, Muggeo M, Crepaldi G, Effect of metformin on insulin-stimulated glucose turnover and insulin binding to receptors in type II diabetes. Diabetes Care 10:62–67, 1991Google Scholar
  180. 180.
    Hother-Nielsen O, Schmitz O, Andersen H, Beck-Nielsen H, Pedersen O, Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes. Acta Endocrinol 120:257–265, 1989Google Scholar
  181. 181.
    DeFronzo RA, Barzilai N, Simonson D, Mechanism of metformin action in obese and lean non-insulin dependent diabetic subjects. J Clin Endocrinol Metab 73:1294–1301, 1991Google Scholar
  182. 182.
    Scarlett J, Gray R, Griffin J, Olefsky J, Kolterman O, Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care 5:353–363, 1982Google Scholar
  183. 183.
    Nankervis A, Proietto J, Aitken P, Harewood M, Alford F, Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in type II (non-insulin dependent), diabetes. Diabetologia 23:320–325, 1982Google Scholar
  184. 184.
    Ginsberg H, Rayfield E, Effect of insulin therapy on insulin resistance in type II diabetic subjects: evidence for heterogenity. Diabetes 30:739–745, 1981Google Scholar
  185. 185.
    Salhanick A, Konowitz P, Amatruda J, Potentiation of insulin action by a sulfonylurea in primary culture of hepatocytes from normal and diabetic rats. Diabetes 32:206–212, 1983Google Scholar
  186. 186.
    Fujita T, Sugiyama Y, Taketomi S, Sohda T, Kawamatsu Y, Iwatsuka H, Suzouki Z, Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-methylcyclohexylmethoxy] benzyl]-thiazolidine-2,4-di one (ADD-3978, U-63,287, ciglitazone), a new antidiabetic agent. Diabetes 32:804–810, 1983Google Scholar
  187. 187.
    Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H, Characterization of new oral antidiabetic agent CS-045: studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 37:1549–1558, 1988Google Scholar
  188. 188.
    Ciaraldi TP, Gilmore A, Olefsky JM, Goldberg M, Heidenreich KA, In vitro studies on the action of CS-045: a new antidiabetic agent. Metabolism 39:1056–1062, 1990Google Scholar
  189. 189.
    Iwamoto Y, Kuzuya T, Matsuda A, Awata T, Kumakura S, Inooka G, Shiraishi I, Effects of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM. Diabetes Care 14:1083–1086, 1991Google Scholar
  190. 190.
    Kraegen EW, James DE, Jenkins AB, Chisholm DJ, Storlein LH, A potent in vivo effect of ciglitazone on muscle insulin resistance induced by high fat feeding in rats. Metabolism 1089–1093, 1989Google Scholar
  191. 191.
    Chang AY, Wyse BM, Gilchrist BJ, Citaglitazone, a new hypoglycemic agent: effects on glucose and lipid metabolisms and insulin binding in the adipose tissue of C5BL/6J-ob/ob and +/? mice. Diabetes 32:839–845, 1983Google Scholar
  192. 192.
    Hoffman CA, Edwards CW, Hilmann RM, Colca JR, Treatment of insulin resistant mice with oral antidiabetic agent pioglitazone: evaluation of liver GLUT2 and phosphoenolpyruvate carboxykinase expression. Endocrinology 130:735–740, 1992Google Scholar
  193. 193.
    Suter SL, Nolan JJ, Wallace P, Gumbiner B, Olefsky JM, Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care 15:193–203, 1992Google Scholar
  194. 194.
    Chiaken RI, Eckert-Norton M, Pasmantier R, Boden G, Ryan I, Gelfand RA, Lebovitz HE, Metabolic effects of darglitazone, and insulin sensitizer, in NIDDM subjects. Diabetologia 38:1307–1312, 1995Google Scholar
  195. 195.
    Nolan JJ, Ludvir P, Beerdsen P, Joyce M, Olefsky J, Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 331:1188–1193, 1994Google Scholar
  196. 196.
    Stevenson RW, McPherson RK, Genereux PE, Danbury BH, Kreutter DK, Antidiabetic agent englitazone enhances insulin action in nondiabetic rats without producing hypoglycemia. Metabolism 40:1268–1274, 1991Google Scholar
  197. 197.
    Kaufman LN, Peterson MM, DeGrange LM, Pioglitazone attenuates diet-induced hypertension in rats. Metabolism 44: 1105–1109, 1995Google Scholar
  198. 198.
    Cohen N, Halberstram M, Shlimovich P, Chang CJ, Shamoon H, Rossetti L, Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 95:2501–2509, 1995Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • A. A. Alzaid
    • 1
  1. 1.Riyadh Armed Forces HospitalRiyadhKingdom of Saudi Arabia

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