Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes.
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.
D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose