Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes

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

Research output: Contribution to journalArticlepeer-review


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 (K(m) 156 with a decreased maximum response (V(max) 320 ± 22 vs. 405 ± 10 mg.m-2.min-1 in nondiabetics, P < 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 < 0.02, and 120 ± 8 vs. 85 ± 4 pg for erythrocytes in nondiabetics, P < 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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
StatePublished - 1984
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology


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