INCREASED GLUCOSE TRANSPORT-PHOSPHORYLATION AND MUSCLE GLYCOGEN-SYNTHESIS AFTER EXERCISE TRAINING IN INSULIN-RESISTANT SUBJECTS

Background Insulin resistance in the offspring of parents with non-ins ulin-dependent diabetes mellitus (NIDDM) is the best predictor of deve lopment of the disease and probably plays an important part in its pat hogenesis. We studied the mechanism and degree to which exercise train ing improves insulin sensitivity in these subjects. Methods Ten adult children of parents with NIDDM and eight normal subjects were studied before starting an aerobic exercise-training program, after one sessio n of exercise, and after six weeks of exercise. Insulin sensitivity wa s measured by the hyperglycemic-hyperinsulinemic clamp technique combi ned with indirect calorimetry, and the rate of glycogen synthesis in m uscle and the intramuscular glucose-6-phosphate concentration were mea sured by carbon-13 and phosphorus-31 nuclear magnetic resonance spectr oscopy, respectively. Results During the base-line study, the mean (+/ -SE) rate of muscle glycogen synthesis was 63+/-9 percent lower in the offspring of diabetic parents than in the normal subjects (P<0.001). The mean value increased 69+/-10 percent (P=0.04) and 62+/-11 percent (P=0.04) after the first exercise session and 102+/-11 percent (P=0.02 ) and 97+/-9 percent (P=0.008) after six weeks of exercise training in the offspring and the normal subjects, respectively. The increment in glucose-6-phosphate during hyperglycemic-hyperinsulinemic clamping wa s lower in the offspring than in the normal subjects (0.039+/-0.013 vs . 0.089+/-0.009 mol per liter, P=0.005), reflecting reduced glucose tr ansport-phosphorylation, but this increment was normal in the offsprin g after the first exercise session and after exercise training. Basal and stimulated insulin secretion was higher in the offspring than the normal subjects and was not altered by the exercise training program. Conclusions Exercise increases insulin sensitivity in both normal subj ects and the insulin-resistant offspring of diabetic parents because o f a twofold increase in insulin-stimulated glycogen synthesis in muscl e, due to an increase in insulin-stimulated glucose transport-phosphor ylation. (C) 1996, Massachusetts Medical society.