Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans - Studies using [O-15]O-2, [O-15]H2O, [F-18]fluoro-deoxy-glucose and positron emission tomography

In vitro studies have shown that insulin and exercise stimulate glucose upt ake in part via distinct mechanisms. We determined whether a high rate of i nsulin-stimulated glucose uptake (good insulin sensitivity) is associated w ith an enhanced ability of exercise to increase glucose uptake in vivo in h umans. In our study, 22 normal subjects performed one-legged isometric exer cise for 105 min (45-150 min) under intravenously maintained euglycemic-hyp erinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood fl ow, and glucose uptake were quantitated simultaneously in skeletal muscle o f both legs using [O-15]O-2, [O-15]H2O, [F-18]fluoro-deoxy-glucose, and pos itron emission tomography. The one-legged exercise, performed at an intensi ty of 11% of maximal isometric force, was designed to induce similar increa ses in oxygen consumption in both groups. In the entire group, exercise inc reased oxygen consumption from 2.3 +/- 0.3 ml . kg(-1) muscle . min(-1) (in sulin) to 34.2 +/- 3. ml . kg(-1) muscle . min(-1) (insulin and exercise) ( P < 0.001) and muscle glucose uptake from 60 +/- 6 mu mol . kg(-1) muscle . min(-1) (insulin) to 220 +/- 22 mu mol . kg(-1) muscle . min(-1) (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose uptake was due to marked increases in blood flow (36 +/- 5 ml . kg(-1) muscle . mi n(-1) [insulin] vs. 262 +/- 20 ml . k(-1) muscle . min(-1) [insulin and exe rcise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/- 0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/l (insulin and exercise) (P < 0.001). The subjects were classified according to their mean rate of whole -body insulin-stimulated glucose uptake into those with high (49 +/- 3 mu m ol . kg(-1) . min(-1)) and normal (27 +/- 2 mu mol . kg(-1) . min(-1)) rate s of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1. 1 vs. 2.3 +/- 1.2 ml . kg(-1) muscle . min(-1), normal vs. high insulin sen sitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml . kg(-1) muscle . min(-1)) rates of oxygen consumption were comparable betwee n the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 +/- 25 mu mol . kg(-1) . muscle. min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 mu mol . kg(-1) musc le . min(-1)) (P < 0.05). Muscle blood flow was closely correlated with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin-stimulated (30 +/- 5 vs. 35 +/- 6 ml . kg(-1) muscle . min(-1)) and exercise-induced i ncrements (222 +/- 31 vs. 228 +/- 23 ml . kg(-1) muscle . min(-1)) in muscl e blood flow were similar between the groups. Glucose extraction remained h igher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05) . We conclude that whereas acute exercise per se increases glucose uptake v ia increasing glucose delivery, good insulin sensitivity modulates exercise -induced increases in glucose uptake by enhancing cellular glucose extracti on.