AJP - Endocrinology and Metabolism, Vol 247, Issue 5 688-E692, Copyright © 1984 by American Physiological Society
Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes
L. J. Mandarino, P. J. Campbell, I. S. Gottesman and J. E. Gerich
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.
