Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography.
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 x kg(-1) muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1) muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x 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 x kg(-1) muscle x min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x 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/1 (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 micromol x kg(-1) x min(-1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1) muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x 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 pmol x kg(-1) muscle x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol x kg(-1) muscle x 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 x kg(-1) muscle x min(-1)) and exercise-induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x 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.
Department of Medicine, University of Turku, Finland. pirjo.nuutila@utu.fi
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P
Nuutila
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P
Peltoniemi
V
V
Oikonen
K
K
Larmola
J
J
Kemppainen
T
T
Takala
H
H
Sipilä
A
A
Oksanen
U
U
Ruotsalainen
G B
GB
Bolli
H
H
Yki-Järvinen
D000328:Adult; D015444:Exercise / Q000502:physiology*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics*; D005082:Physical Exertion / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed; D014867:Water / Q000378:metabolism
D007328:Insulin; D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; D014867:Water; D019788:Fluorodeoxyglucose F18; D005947:Glucose