INSULIN-STIMULATED MUSCLE GLUCOSE CLEARANCE IN PATIENTS WITH NIDDM - EFFECTS OF ONE-LEGGED PHYSICAL-TRAINING

Physical training increases insulin action in skeletal muscle in healt hy men. In non-insulin-dependent diabetes mellitus (NIDDM), only minor improvements in whole-body insulin action are seen. We studied the ef fect of training on insulin-mediated glucose clearance rates (GCRs) in the whole body and in leg muscle in seven patients with NIDDM and in eight healthy control subjects. One-legged training was performed for 10 weeks. GCR in whole body and in both legs were measured before, the day after, and 6 days after training by hyperinsulinemic (28, 88, and 480 mU . min(-1). m(-2)), isoglycemic clamps combined with the leg ba lance technique. On the 5th day of detraining, one bent of exercise wa s performed with the nontraining leg. Muscle biopsies were obtained be fore and after training. Whole-body GCRs were always lower (P < 0.05) in NIDDM: patients compared with control subjects and increased (P < 0 .05) in response to training. In untrained muscle, GCR was lower (P < 0.05) in NIDDM patients (13 +/- 4, 91 +/- 9, and 148 +/- 12 ml/min) co mpared with control subjects (56 +/- 12, 126 +/- 14, and 180 +/- 14 ml /min). It increased (P < 0.05) in both groups in response to training (43 +/- 10, 144 +/- 17, and 205 +/- 24 [NIDDM patients] and 84 +/- 10, 212 +/- 20, and 249 +/- 16 ml/min [control subjects]). Acute exercise did not increase leg GCR. In NIDDM patients, the effect of training w as lost after 6 days, while the effect lasted longer in control subjec ts. Training increased CP < 0.05) muscle lactate production and glucos e storage as well as glycogen synthase (GS) mRNA in both groups. We co nclude that training increases insulin action in skeletal muscle in co ntrol subjects and NIDDM patients, and in NIDDM patients normal values may be obtained. The increase in gained muscle cannot fully account f or the increase in whole-body GCR. Improvements in GCR involve enhance ment of insulin-mediated increase in muscle blood flow and the ability to extract glucose. They are accompanied by enhanced nonoxidative glu cose disposal and increases in GS mRNA. The improvements in insulin ac tion are short-lived.