To characterize the ability of insulin to activate the skeletal muscle metabolic pathways of glucose storage, oxidation, and glycolysis in normal weight patients with NIDDM and nondiabetic volunteer subjects closely matched for age, sex, relative weight, and body composition.
Ten patients with NIDDM (body mass index 23.9 ± 0.74 kg/m2) and 8 nondiabetic volunteer subjects (body mass index 23.4 ± 0.41 kg/m2) were studied. Leg muscle glucose uptake, non-oxidized glycolysis, glucose oxidation, and glucose storage were determined during euglycemic-hyperinsulinemic clamp experiments using the leg balance technique combined with leg indirect calorimetry. Percutaneous muscle biopsies were obtained to assay insulin stimulation of muscle glycogen synthase activity as a biochemical marker of insulin action.
During hyperinsulinemic clamp experiments, leg glucose uptake was equivalent in NIDDM patients and nondiabetic subjects (6.38 ± 1.14 vs. 6.41 ± 0.73 μmol.min−1 · 100 ml tissue−1), as were rates of leg glucose oxidation (1.63 ± 0.25 vs. 2.14 ± 0.17 μmol.min−1 · 100 ml tissue−1) and leg glucose storage (4.35 ± 1.10 vs. 3.48 ± 0.65 μmol·min−1 · 100 ml tissue−1). The combined net balance of lactate and Ala (non-oxidized glycolysis) was lower in NIDDM patients (−0.39 ± 0.06 vs. −0.79 ± 0.11 μmol·min−1 · 100 ml tissue−1, P = 0.01). Muscle glycogen synthase was activated to a similar extent during the hyperinsulinemic clamp in NIDDM patients and nondiabetic volunteer subjects, through basal glycogen synthase activity was lower in NIDDM patients. Nondiabetic subjects and NIDDM patients who were withdrawn from sulfonylurea therapy had impaired insulin secretion during a 75-g oral glucose tolerance test, with similar basal levels as nondiabetic subjects (54 ± 12 vs. 42 ± 6 pM), but reduced peak insulin levels (126 ± 30 vs. 468 ± 102 pM, P < 0.01).
Detailed in vivo and in vitro assessment of insulin regulation of skeletal muscle glucose metabolism in lean NIDDM patients indicates that insulin action is intact in the muscle tissue of these patients.