AJP - Endocrinology and Metabolism, Vol 261, Issue 1 E132-E140, Copyright © 1991 by American Physiological Society
Dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus
R. R. Henry, A. W. Thorburn, P. Beerdsen and B. Gumbiner
Department of Medicine, University of California, San Diego.
To determine the dose-response characteristics of impaired glucose
oxidation in non-insulin-dependent diabetes mellitus (NIDDM), indirect
calorimetry was performed on eight matched control and NIDDM subjects
during the basal state and during three glucose clamps at insulin infusion
rates of 150, 300, and 1,500 pmol.m-2.min-1. Hyperglycemia was used to
achieve matched rates of glucose uptake at each insulin infusion. Glucose
uptake in the basal state was greater in NIDDM [3.75 +/- 0.23 vs. 2.50 +/-
0.10 mg.kg fat-free mass (FFM)-1.min-1, P less than 0.005] but was similar
at approximately 8, 12, and 26 mg.kg FFM-1.min-1 at each insulin infusion.
Basal protein oxidation, fat oxidation, and plasma free fatty acids were
similar and equally sensitive to suppression by insulin in both groups.
Glucose oxidation was reduced 20-26%, and circulating lactate increased
50-90% at physiological but not at pharmacological insulin concentrations
in NIDDM. The dose-response relationship between serum insulin and glucose
oxidation was right shifted in NIDDM with half-maximal activation at 368
+/- 91 vs. 179 +/- 27 pM in controls (P less than 0.05). In conclusion,
glucose oxidation is reduced at physiological insulin concentrations in
NIDDM and cannot be explained by concomitant obesity, increased fat
oxidation, or reduced glucose uptake but results from impaired sensitivity
to stimulation by insulin, possibly at pyruvate dehydrogenase.
