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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1979 May; 63(5): 939–946.
doi: 10.1172/JCI109394
PMCID: PMC372035
PMID: 376552

This article has been retracted.
Retraction in: Diabetes. 1980 August; 29(8): 672    See also: PMC Retraction Policy

Insulin Sensitivity and Insulin Binding to Monocytes in Maturity-Onset Diabetes

Ralph Defronzo, David Deibert, Rosa Hendler, Philip Felig, and Vijay Soman
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Abstract

Tissue sensitive to insulin and insulin binding to monocytes were evaluated in 15 nonobese maturity-onset diabetics and in 16 healthy controls. Insulin sensitivity was determined by the insulin clamp technique in which the plasma insulin is acutely raised and maintained 100 μU/ml above the fasting level and plasma glucose is held constant at fasting levels by a variable glucose infusion. The amount of glucose infused is a measure of overall tissue sensitivity to insulin.

In the diabetic group, the fasting plasma glucose concentration (168±4 mg/dl) was 85% greater than controls (P < 0.01) whereas the plasma insulin level (15±1 μU/ml) was similar to controls. During the insulin clamp study, comparable plasma insulin levels were achieved in the diabetics (118±5) and the controls (114±5 μU/ml). However, the glucose infusion rate in the diabetics (4.7±0.4 mg/kg·min) was 30% below controls (P < 0.01). Among the diabetics, the glucose infusion rate correlated directly with the fasting plasma glucose level (r = 0.57, P < 0.05). In five diabetic subjects, glucose metabolism was similar to controls, and these diabetics had the highest fasting glucose levels. When they were restudied after prior normalization (with insulin) of the fasting plasma glucose (100±1 mg/dl), the glucose infusion rate during the insulin clamp was 30% lower than observed in association with hyperglycemia (P < 0.01). Studies that employed tritiated glucose to measure endogenous glucose production indicated comparable 90-95% inhibition of hepatic glucose production during hyperinsulinemia in the diabetic and control subjects.

125I-insulin binding to monocytes in the diabetics (5.5±0.6%) was 30% below that in controls (P < 0.01). Insulin binding to monocytes and insulin action as determined with the insulin clamp were highly correlated in both control (r = 0.67, P < 0.01), and diabetic subjects (r = 0.88, P < 0.001).

We conclude that (a) tissue sensitivity to physiologic hyperinsulinemia is reduced in most maturity-onset diabetics; (b) this decrease in sensitivity is located, at least in part, in extrahepatic tissues; (c) the resistance to insulin may be mediated by a reduction in insulin binding; and (d) in maturity-onset diabetics with normal tissue sensitivity to insulin, hyperglycemia may be a contributing factor to the normal rates of insulin-mediated glucose uptake.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  • Sherwin R, Felig P. Pathophysiology of diabetes mellitus. Med Clin North Am. 1978 Jul;62(4):695–711. [PubMed] [Google Scholar]
  • Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest. 1967 Dec;46(12):1954–1962. [PMC free article] [PubMed] [Google Scholar]
  • Bagdade JD, Bierman EL, Porte D., Jr The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest. 1967 Oct;46(10):1549–1557. [PMC free article] [PubMed] [Google Scholar]
  • Reaven G, Miller R. Study of the relationship between glucose and insulin responses to an oral glucose load in man. Diabetes. 1968 Sep;17(9):560–569. [PubMed] [Google Scholar]
  • Reaven GM, Shen SW, Silvers A, Farquhar JW. Is there a delay in the plasma insulin response of patients with chemical diabetes mellitus? Diabetes. 1971 Jun;20(6):416–423. [PubMed] [Google Scholar]
  • Chiles R, Tzagournis M. Excessive serum insulin response to oral glucose in obesity and mild diabetes. Study of 501 patients. Diabetes. 1970 Jun;19(6):458–464. [PubMed] [Google Scholar]
  • Danowski TS, Khurana RC, Nolan S, Stephan T, Gegick CG, Chae S, Vidalon C. Insulin patterns in equivocal glucose tolerance tests (chemical diabetes). Diabetes. 1973 Nov;22(11):808–812. [PubMed] [Google Scholar]
  • Tchobroutsky G, Kopf A, Eschwege E, Assan R. Serial postprandial plasma insulin levels in 117 subjects with and without diabetes. Diabetes. 1973 Nov;22(11):825–833. [PubMed] [Google Scholar]
  • Alford FP, Martin FI, Pearson MJ. The significance and interpretation of mildly abnormal oral glucose tolerance. Diabetologia. 1971 Jun;7(3):173–180. [PubMed] [Google Scholar]
  • Garber AJ, Cryer PE, Santiago JV, Haymond MW, Pagliara AS, Kipnis DM. The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. J Clin Invest. 1976 Jul;58(1):7–15. [PMC free article] [PubMed] [Google Scholar]
  • Reaven GM, Bernstein R, Davis B, Olefsky JM. Nonketotic diabetes mellitus: insulin deficiency or insulin resistance? Am J Med. 1976 Jan;60(1):80–88. [PubMed] [Google Scholar]
  • 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. 1970 Dec;49(12):2151–2160. [PMC free article] [PubMed] [Google Scholar]
  • Ginsberg H, Olefsky JM, Reaven GM. Further evidence that insulin resistance exists in patients with chemical diabetes. Diabetes. 1974 Aug;23(8):674–678. [PubMed] [Google Scholar]
  • 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 Mar;55(3):454–461. [PMC free article] [PubMed] [Google Scholar]
  • WALAAS O, WALAAS E. Effect of epinephrine on rat diaphragm. J Biol Chem. 1950 Dec;187(2):769–776. [PubMed] [Google Scholar]
  • Altszuler N, Steele R, Rathgeb I, De Bodo RC. Glucose metabolism and plasma insulin level during epinephrine infusion in the dog. Am J Physiol. 1967 Mar;212(3):677–682. [PubMed] [Google Scholar]
  • Plekhanov VA, Goreva OA, Shcherbakov VI. O roli visochnykh oblastei v uslovnoreflektornoi deiatel'nosti posle pererezki ruchek zadnego dvukholmiia. Zh Vyssh Nerv Deiat Im I P Pavlova. 1975 Sep-Oct;25(5):962–966. [PubMed] [Google Scholar]
  • 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. 1977 Nov;45(5):1124–1127. [PubMed] [Google Scholar]
  • Saccà L, Sherwin R, Felig P. Influence of somatostatin on glucagon- and epinephrine-stimulated hepatic glucose output in the dog. Am J Physiol. 1979 Feb;236(2):E113–E117. [PubMed] [Google Scholar]
  • Sherwin RS, Kramer KJ, Tobin JD, Insel PA, Liljenquist JE, Berman M, Andres R. A model of the kinetics of insulin in man. J Clin Invest. 1974 May;53(5):1481–1492. [PMC free article] [PubMed] [Google Scholar]
  • Olefsky JM, Reaven GM. Insulin binding in diabetes. Relationships with plasma insulin levels and insulin sensitivity. Diabetes. 1977 Jul;26(7):680–688. [PubMed] [Google Scholar]
  • DeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P. Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest. 1978 Jul;62(1):204–213. [PMC free article] [PubMed] [Google Scholar] Retracted
  • Sherwin RS, Hendler R, DeFronzo R, Wahren J, Felic P. Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin. Proc Natl Acad Sci U S A. 1977 Jan;74(1):348–352. [PMC free article] [PubMed] [Google Scholar]
  • Hers HG. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. [PubMed] [Google Scholar]
  • DeFronzo RA, Ferrannini E, Hendler R, Wahren J, Felig P. Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5173–5177. [PMC free article] [PubMed] [Google Scholar]
  • Gavin JR, 3rd, Gorden P, Roth J, Archer JA, Buell DN. Characteristics of the human lymphocyte insulin receptor. J Biol Chem. 1973 Mar 25;248(6):2202–2207. [PubMed] [Google Scholar]
  • Wise JK, Hendler R, Felig P. Influence of glucocorticoids on glucagon secretion and plasma amino acid concentrations in man. J Clin Invest. 1973 Nov;52(11):2774–2782. [PMC free article] [PubMed] [Google Scholar]
  • Gavin JR, 3rd, Roth J, Neville DM, Jr, de Meyts P, Buell DN. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci U S A. 1974 Jan;71(1):84–88. [PMC free article] [PubMed] [Google Scholar]
  • Olefsky JM, Reaven GM. Decreased insulin binding to lymphocytes from diabetic subjects. J Clin Invest. 1974 Dec;54(6):1323–1328. [PMC free article] [PubMed] [Google Scholar]
  • Olefsky JM. The insulin receptor: its role in insulin resistance of obesity and diabetes. Diabetes. 1976 Dec;25(12):1154–1162. [PubMed] [Google Scholar]
  • Roth J, Kahn CR, Lesniak MA, Gorden P, De Meyts P, Megyesi K, Neville DM, Jr, Gavin JR, 3rd, Soll AH, Freychet P, et al. Receptors for insulin, NSILA-s, and growth hormone: applications to disease states in man. Recent Prog Horm Res. 1975;31:95–139. [PubMed] [Google Scholar]
  • Olefsky JM, Reaven GM. Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients. Am J Med. 1976 Jan;60(1):89–95. [PubMed] [Google Scholar]
  • Soman V, Tamborlane W, DeFronzo R, Genel M, Felig P. Insulin binding and insulin sensitivity in isolated growth hormone deficiency. N Engl J Med. 1978 Nov 9;299(19):1025–1030. [PubMed] [Google Scholar]
  • Navalesi R, Pilo A, Ferrannini E. Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin. J Clin Invest. 1978 Jan;61(1):197–208. [PMC free article] [PubMed] [Google Scholar]
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