Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes.

L. J. Mandarino, P. J. Campbell, I. S. Gottesman, J. E. Gerich

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Abstract

By use of the glucose clamp sequential insulin infusion technique, we compared the dose-response characteristics of insulin-mediated glucose disposal in 17 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 13 age- and weight-matched nondiabetic volunteers. In terms of plasma insulin concentrations, the dose-response curve in the diabetics was shifted to the right (Km 156 +/- 28 vs. 58 +/- 4 microU/ml in nondiabetics, P less than 0.01) with a decreased maximum response (Vmax 320 +/- 22 vs. 405 +/- 10 mg X m-2 X min-1 in nondiabetics, P less than 0.01). Moreover, coupling between insulin receptor binding and activation of insulin effector units was defective in the diabetic subjects (half-maximally effective insulin receptor occupancy 184 +/- 11 vs. 145 +/- 12 pg in nondiabetics for monocytes, P less than 0.02, and 120 +/- 8 vs. 85 +/- 4 pg for erythrocytes in nondiabetics, P less than 0.01). The presence of defective coupling in itself could explain the abnormal insulin dose-response characteristics for glucose disposal in NIDDM and differentiates the insulin resistance of this condition from that of obesity in which coupling is normal.

Original languageEnglish (US)
JournalThe American journal of physiology
Volume247
Issue number5 Pt 1
StatePublished - Nov 1984
Externally publishedYes

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Insulin Receptor
Insulin
Type 2 Diabetes Mellitus
Glucose
Glucose Clamp Technique
Insulin Resistance
Monocytes
Volunteers
Obesity
Erythrocytes
Weights and Measures

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mandarino, L. J., Campbell, P. J., Gottesman, I. S., & Gerich, J. E. (1984). Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. The American journal of physiology, 247(5 Pt 1).

Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. / Mandarino, L. J.; Campbell, P. J.; Gottesman, I. S.; Gerich, J. E.

In: The American journal of physiology, Vol. 247, No. 5 Pt 1, 11.1984.

Research output: Contribution to journalArticle

Mandarino, LJ, Campbell, PJ, Gottesman, IS & Gerich, JE 1984, 'Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes.', The American journal of physiology, vol. 247, no. 5 Pt 1.
Mandarino LJ, Campbell PJ, Gottesman IS, Gerich JE. Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. The American journal of physiology. 1984 Nov;247(5 Pt 1).
Mandarino, L. J. ; Campbell, P. J. ; Gottesman, I. S. ; Gerich, J. E. / Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. In: The American journal of physiology. 1984 ; Vol. 247, No. 5 Pt 1.
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