Enhanced stimulation of glucose uptake by increases exercise-stimulated gluco se uptake in skeletal muscle in humans studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography

Abstract

In vitro studies have shown that insulin and exercise stimulate glucose uptake in part via distinct mechanisms. We determined whether a high rate of insulin-stimulated glucose uptake (good insulin sensitivity) is associated with an enhanced ability of exercise to increase glucose uptake in vivo in humans. In our study, 22 normal subjects performed one-legged isometric exercise for 105 min (45-150 min) under intravenously maintained euglycemic- hyperinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood flow, and glucose uptake were quantitated simultaneously in skeletal muscle of both legs using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one-legged exercise, performed at an intensity of 11% of maximal isometric force, was designed to induce similar increases in oxygen consumption in both groups. In the entire group, exercise increased oxygen consumption from 2.3 ± 0.3 ml · kg-1 muscle · min-1 (insulin) to 34.2 ± 3. ml · kg-1 muscle · min-1 (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 ± 6 μmol · kg-1 muscle · min-1 (insulin) to 220 ± 22 μmol · 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 · min-1 [insulin] vs. 262 ± 20 ml · kg-1 muscle · min-1 [insulin and exercise], 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 μmol · kg-1 · min-1) and normal (27 ± 2 μmol · kg-1 · min-1) rates 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 sensitivity) and exercise- and insulin-stimulated (33 ± 6 vs. 34 ± 4 ml ± kg-1 muscle · min-1) rates of oxygen consumption were comparable between the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 ± 25 μmol · kg-1 muscle · min-1) than in the group with normal insulin sensitivity (125 · 19 μmol · kg-1 muscle, 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 increments (222 ± 31 vs. 228 ± 23 ml · kg-1 muscle · min-1) in muscle blood flow were similar between the groups. Glucose extraction remained higher 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 via increasing glucose delivery, good insulin sensitivity modulates exercise-induced increases in glucose uptake by enhancing cellular glucose extraction.