METABOLIC PATHWAYS OF GLUCOSE IN SKELETAL-MUSCLE OF LEAN NIDDM PATIENTS

OBJECTIVE - To characterize the ability of insulin to activate the ske letal muscle metabolic pathways of glucose storage, oxidation, and gly colysis in normal weight patients with NIDDM and nondiabetic volunteer subjects closely matched for age, sex, relative weight, and body comp osition. RESEARCH DESIGN AND METHODS - Ten patients with NIDDM (body m ass index 23.9 +/- 0.74 kg/m2) and 8 nondiabetic volunteer subjects (b ody mass index 23.4 +/- 0.41 kg/m2) were studied. Leg muscle glucose u ptake, nonoxidized glycolysis, glucose oxidation, and glucose storage were determined during euglycemic-hyperinsulinemic clamp experiments u sing the leg balance technique combined with leg indirect calorimetry. Percutaneous muscle biopsies were obtained to assay insulin stimulati on of muscle glycogen synthase activity as a biochemical marker of ins ulin action. RESULTS - During hyperinsulinemic clamp experiments, leg glucose uptake was equivalent in NIDDM patients and nondiabetic subjec ts (6.38 +/- 1.14 vs. 6.41 +/- 0.73 mumol . min - 1 - 1 00 ml tissue - 1), as were rates of leg glucose oxidation (1.63 +/- 0.25 vs. 2.14 +/ - 0.17 mumol . min-1 - 100 ml tissue-1) and leg glucose storage (4.35 +/- 1.10 vs. 3.48 +/- 0.65 mumol . min-1 . 100 ml tissue-1). The combi ned net balance of lactate and Ala (nonoxidized glycolysis) was lower in NIDDM patients (-0.39 +/- 0.06 vs. -0.79 +/- 0.11 mumol . min-1 . 1 00 ml tissue-1, P = 0.01). Muscle glycogen synthase was activated to a similar extent during the hyperinsulinemic clamp in NIDDM patients an d nondiabetic volunteer subjects, through basal glycogen synthase acti vity was lower in NIDDM patients. Nondiabetic subjects and NIDDM patie nts who were withdrawn from sulfonylurea therapy had impaired insulin secretion during a 75-g oral glucose tolerance test, with similar basa l levels as nondiabetic subjects (54 +/- 12 vs. 42 +/- 6 pM), but redu ced peak insulin levels (126 +/- 30 vs. 468 +/- 102 pM, P < 0.01). CON CLUSIONS - Detailed in vivo and in vitro assessment of insulin regulat ion of skeletal muscle glucose metabolism in lean NIDDM patients indic ates that insulin action is intact in the muscle tissue of these patie nts.