Exercise restores skeletal muscle glucose delivery but not insulin-mediated glucose transport and phosphorylation in obese subjects.
OBJECTIVE
Insulin resistance in obese subjects results in the impaired disposal of glucose by skeletal muscle. The current study examined the effects of insulin and/or exercise on glucose transport and phosphorylation in skeletal muscle and the influence of obesity on these processes.


METHODS
Seven obese and 12 lean men underwent positron emission tomography with 2-deoxy-2-[(18)F]fluoro-d-glucose in resting and isometrically exercising skeletal muscle during normoglycemic hyperinsulinemia. Data were analyzed by two-tissue compartmental modeling. Perfusion and oxidative capacity were measured during insulin stimulation by [15O]H2O and [15O]O2.


RESULTS
Exercise increased glucose fractional uptake (K), inward transport rate (K(1)), and the k(3) parameter, combining transport and intracellular phosphorylation, in lean and obese subjects. In each group, there was no statistically significant difference between plasma flow and K(1). At rest, a significant defect in K(1) (P = 0.0016), k(3) (P = 0.016), and K (P = 0.022) was found in obese subjects. Exercise restored K(1), improved but did not normalize K (P = 0.03 vs. lean), and did not ameliorate the more than 60% relative impairment in k(3) in obese individuals (P = 0.002 vs. lean). The glucose oxidative potential tended to be reduced by obesity.


CONCLUSIONS
The study indicates that exercise restores the impairment in insulin-mediated skeletal muscle perfusion and glucose delivery associated with obesity but does not normalize the defect involving the proximal steps regulating glucose disposal in obese individuals. Our data support the use of 2-deoxy-2-[18F]fluoro-d-glucose-positron emission tomography in the dissection between substrate supply and intrinsic tissue metabolism.
Slimani
L
L
Turku PET Centre, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland.
Oikonen
V
V
Hällsten
K
K
Savisto
N
N
Knuuti
J
J
Nuutila
P
P
Iozzo
P
P
D000328:Adult; D001692:Biological Transport; D015444:Exercise / Q000502:physiology*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D052097:Quadriceps Muscle / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D007328:Insulin; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose