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The Pathophysiological Consequences of Adipose Tissue Insulin Resistance

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Part of the book series: Contemporary Endocrinology ((COE,volume 12))

Abstract

The relationship between insulin resistance and adipose tissue is exceedingly complex. At the simplest level, as discussed in the subsequent section, even the meaning of “insulin resistance” in this context is not totally clear. In order to focus this review on the relationship between adipose tissue and insulin resistance, it will be organized as an answer to the two following fundamental questions: 1) Do differences in the ability of insulin to regulate adipose tissue exist between individuals? and 2) If so, what are the metabolic consequences of these differences in insulin action on adipose tissue?

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References

  1. DeFronzo RA, Tobin J, Andres R. The glucose clamp technique. A method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: 214–223.

    Google Scholar 

  2. Greenfield MS, Doberne L, Kraemer FB, Tobey TA, Reaven GM. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes 1981; 30: 387–392.

    Article  PubMed  CAS  Google Scholar 

  3. Björntorp P, Sjöström L. Carbohydrate storage in man: speculations and some quantitative considerations. Metabolism 1978; 27 (Suppl 2): 1853–1865.

    Article  PubMed  Google Scholar 

  4. Swislocki ALM, Chen Y-DI, Golay A, Chang M-O, Reaven GM. Insulin suppression of plasma-free fatty acid concentration in normal individuals and patients with Type 2 (non-insulin-dependent) diabetes. Diabetologia 1987; 30: 622–626.

    PubMed  CAS  Google Scholar 

  5. Pei D, Chen Y-DI, Hollenbeck CB, Bhargava R, Reaven GM. Relationship between insulin-mediated glucose disposal by muscle and adipose tissue lipolysis in healthy volunteers. J Clin Endocrinol Metab 1995; 80: 3368–3372.

    Article  PubMed  CAS  Google Scholar 

  6. Chen Y-DI, Golay A, Swislocki ALM, Reaven GM. Resistance to suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1987; 64: 17–21.

    Article  PubMed  CAS  Google Scholar 

  7. Ginsberg H, Kimmerling G, Olefsky JM, Reaven GM. Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. J Clin Invest 1975; 55: 454–461.

    Article  PubMed  CAS  Google Scholar 

  8. Reaven GM. Insulin resistance in non-insulin-dependent diabetes mellitus. Does it exist and can it be measured ? Am J Med 1983; 74: 3–17.

    Article  PubMed  CAS  Google Scholar 

  9. Shen S-W, Reaven GM, Farquhar JW. Comparison of impedance to insulin mediated glucose uptake in normal and diabetic subjects. J Clin Invest 1970; 49: 2151–2160.

    Article  PubMed  CAS  Google Scholar 

  10. Ginsberg H, Olefsky JM, Reaven GM. Further evidence that insulin resistance exists in patients with chemical diabetes. Diabetes 1974; 23: 674–678.

    PubMed  CAS  Google Scholar 

  11. Laws A, Stefanick ML, Reaven GM. Insulin resistance and hypertriglyceridemia in nondiabetic relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1989; 69: 343–347.

    Article  PubMed  CAS  Google Scholar 

  12. Ho LT, Chang ZY, Wang JT, Li SH, Liu YF, Chen Y-DI, Reaven GM. Insulin insensitivity in offspring of parents with Type 2 diabetes mellitus. Diabetic Med 1990; 7: 31–34.

    Article  PubMed  CAS  Google Scholar 

  13. Hollenbeck CB, Reaven GM. Variations in insulin stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987; 64: 1169–1173.

    Article  PubMed  CAS  Google Scholar 

  14. Reaven GM, Brand RJ, Chen Y-DI, Mathur AK, Goldfine I. Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals. Diabetes 1993; 42: 1324–1332.

    Article  PubMed  CAS  Google Scholar 

  15. Reaven GM, Hollenbeck CB, Chen Y-DI. Relationship between glucose tolerance, insulin secretion, and insulin action in non-obese individuals with varying degrees of glucose tolerance. Diabetologia 1989; 32: 52–55.

    Article  PubMed  CAS  Google Scholar 

  16. Reaven GM, Chen Y-DI, Hollenbeck CB, Sheu WHH, Ostrega D, Polonsky KS. Plasma insulin, C-peptide, and proinsulin c concentrations in obese and nonobese individuals with varying degrees of glucose tolerance. J Clin Endocrinol Metab 1993; 76: 44–48.

    Article  PubMed  CAS  Google Scholar 

  17. Reaven GM, Hollenbeck CB, Jeng C-Y, Wu MS, Chen Y-Dl. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 1988; 37: 1020–1024.

    Article  PubMed  CAS  Google Scholar 

  18. Pelkonen R, Miettinen A, Taskinen M-R, Nikkila EA. Effect of acute elevation of plasma glycerol, triglyceride and FFA levels on glucose utilization and plasma insulin. Diabetes 1968; 17: 76–82.

    PubMed  CAS  Google Scholar 

  19. Malaisse WJ, Malaisse-Lagae F. Stimulation of insulin secretion by non-carbohydrate metabolites. J Lab Clin Med 1968; 72: 438–448.

    PubMed  CAS  Google Scholar 

  20. Crespin SR, Greenough WB, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids. J Clin Invest 1973; 52: 1979–1984.

    Article  PubMed  CAS  Google Scholar 

  21. Sako Y, Grill V. A 48-h lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and 13-cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology 1990; 127: 1580–1589.

    Article  PubMed  CAS  Google Scholar 

  22. Zhou YP, Grill V. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 1994; 93: 870–876.

    Article  PubMed  CAS  Google Scholar 

  23. Zhou YP, Grill V. Long-term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans. J Clin Endocrinol Metab 1995; 80: 1575–1560.

    Article  Google Scholar 

  24. Zhou YP, Grill V. Palmitate-induced 13-cell insensitivity to glucose is coupled to decreased pyruvate dehyrogenase activity and enhanced kinase activity in rat pancreatic islets. Diabetes 1995; 44: 394–399.

    Article  PubMed  CAS  Google Scholar 

  25. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 1995; 44: 863–870.

    Article  PubMed  CAS  Google Scholar 

  26. 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: 785–789.

    Article  PubMed  CAS  Google Scholar 

  27. Thiébaud D, De Fronzo RA, Jacot E, et al. Effect of long-chain triglyceride infusion on glucose metabolism in man. Metabolism 1982; 31: 1128–1136.

    Article  PubMed  Google Scholar 

  28. Ferrannini E, Barret EJ, Bevilacqua S, DeFronzo RA. Effect of fatty acids on glucose production and utilization in man. J Clin Invest 1983; 72: 1737–1747.

    Article  PubMed  CAS  Google Scholar 

  29. Bevilacqua S, Buzzigoli G, Bonadonna R, Brandi S, Oleggini M, Boni C, Geloni M, Ferrannini E. Operation of Randle’s cycle in patients with NIDDM. Diabetes 1990; 39: 383–389.

    Article  PubMed  CAS  Google Scholar 

  30. Boden G, Chen X, Ruiz J, White JV, Rossetti L. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 1994; 93: 2438–2446.

    Article  PubMed  CAS  Google Scholar 

  31. Boden M, Price TB, Perseghin G, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996; 97: 2859–2865.

    Article  Google Scholar 

  32. Jeng C-Y, Fuh MM-T, Sheu WH-H, Chen Y-DI, Reaven GM. Hormone and substrate modulation of plasma triglyceride concentration in primary hypertriglyceridemia. Endocrinol Metab 1994; 1: 15–21.

    CAS  Google Scholar 

  33. Boden G, Chen X. Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. J Clin Invest 1995; 96: 1261–1268.

    Article  PubMed  CAS  Google Scholar 

  34. Foley JE. Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. Diabetes Care 1992; 15: 773–781.

    Article  PubMed  CAS  Google Scholar 

  35. DeFronzo RA, SimonsonD, Ferrannini E. Hepatic and peripheral insulin resistance: a common feature of Type 2 (non-insulin-dependent) and Type 1 (insulin dependent) diabetes mellitus. Diabetologia 1982; 23: 313–319.

    CAS  Google Scholar 

  36. Nankervis A, Proietto J, Aitken P, Harewood M, Alford F. Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes. Diabetologia 1982; 23: 320–325.

    Article  PubMed  CAS  Google Scholar 

  37. Best J, Judzewitsch R, Pfeifer M, Beard J, Kolter J, Porte Jr D. The effect of chronic sulfonylurea therapy on hepatic glucose production in noninsulin dependent diabetes. Diabetes 1982; 31: 333–338.

    Article  PubMed  CAS  Google Scholar 

  38. Firth RG, Bell PM. Marsh HM, Hansen I, Rizz RA. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extra hepatic tissues. J Clin Invest 1986; 77: 1525–1532.

    Article  PubMed  CAS  Google Scholar 

  39. Campbell PJ, Mandarin LJ, Gerich JE. Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. Metabolism 1988; 37: 15–21.

    Article  PubMed  CAS  Google Scholar 

  40. Chen Y-DI, Jeng C-Y, Hollenbeck CB, Wu M-S, Reaven GM. Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes. J Clin Invest 1988; 82: 21–15.

    Article  PubMed  CAS  Google Scholar 

  41. Chen Y-DI, Swislocki ALM, Jeng C-Y, Juang J-H, Reaven GM. Effect of time on measurement of hepatic glucose production. J Clin Endocrinol Metab 1988; 67: 1084–1088.

    Article  PubMed  CAS  Google Scholar 

  42. Hother-Nielsen O, Beck-Nielsen H. On the determination of basal glucose production rate in patients with Type 2 (non-insulin-dependent) diabetes mellitus using primed-continuous 3–3H-glucose infusion. Diabetologia 1990; 33: 603–610.

    Article  PubMed  CAS  Google Scholar 

  43. Hother-Nielsen O, Beck-Nielsen H. Insulin resistance, but normal basal rates of glucose production in patients with newly diagnosed mild diabetes mellitus. Acta Endocr 1991; 124: 637–645.

    PubMed  CAS  Google Scholar 

  44. Jeng C-Y, Sheu WH-H, Fuh MM-T, Chen Y-DI, Reaven GM. Relationship between hepatic glucose production and fasting plasma glucose concentration in patients with non-insulin-dependent diabetes mellitus. Diabetes 1994; 48: 1440–1444.

    Article  Google Scholar 

  45. Reaven GM, Mondon CE. Effect of in vivo plasma insulin levels on the relationship between perfusate free fatty acid concentration and triglyceride secretion by perfused rat livers. Horm Metab Res 1984; 16: 230–232.

    Article  PubMed  CAS  Google Scholar 

  46. Greenfield M, Koltermann O, Olefsky J, Reaven GM. Mechanism of hypertriglyceridemia in diabetic patients with fasting hyperglycemia. Diabetologia 1980; 18: 441–446.

    Article  PubMed  CAS  Google Scholar 

  47. Reaven GM, Greenfield MS. Diabetic hypertriglyceridemia: evidence for three clinicals syndromes. Diabetes 1981; 30: 66–75.

    PubMed  CAS  Google Scholar 

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© 1999 Springer Science+Business Media New York

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Reaven, G.M. (1999). The Pathophysiological Consequences of Adipose Tissue Insulin Resistance. In: Reaven, G.M., Laws, A. (eds) Insulin Resistance. Contemporary Endocrinology, vol 12. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-716-1_12

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  • DOI: https://doi.org/10.1007/978-1-59259-716-1_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-086-1

  • Online ISBN: 978-1-59259-716-1

  • eBook Packages: Springer Book Archive

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