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Evidence for Spatial Heterogeneity in Insulin- and Exercise-Induced Increases in Glucose Uptake: Studies in Normal Subjects and Patients with Type 1 Diabetes

Turku PET Centre (P.P., H.L., V.O., K.K., O.R., M.J.K., P.N.) and Department of Medicine (H.L., T.R., P.N.), University of Turku, FIN-20520 Turku, Finland; and Department of Medicine (H.Y.-J.), University of Helsinki, FIN-00014 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. Pauliina Peltoniemi, Turku PET Centre, University of Turku, P.O. Box 52, FIN-20520 Turku, Finland. E-mail: papelto{at}utu.fi

Abstract

It is unknown whether resistance to insulin- or exercise-stimulated glucose uptake reflects a spatially uniform or nonuniform decrease in glucose uptake within skeletal muscle. We compared the distributions of muscle glucose uptake and blood flow in eight patients with type 1 diabetes (age 24 ± 1 yr, body mass index 22.0 ± 0.8 kg/m²) and seven age- and weight-matched normal subjects using positron emission tomography, [¹⁸F]-fluoro-deoxy-glucose, and [¹⁵O]-water. Both groups were studied during euglycemic hyperinsulinemia and one-legged exercise. Heterogeneity was evaluated by calculating relative dispersion (SD divided by mean * 100%) of glucose uptake (RD_g) and flow (RD_f) in all pixels within a region of interest in femoral muscle. At rest insulin-stimulated glucose uptake was significantly lower in the type 1 diabetic patients (42 ± 7 µmol/kg per min) than in the normal subjects (78 ± 9 µmol/kg per min, P < 0.001), while muscle blood flows were similar (26 ± 1 vs. 31 ± 3 ml/kg muscle per min, respectively). The exercise-induced increment in glucose uptake but not in blood flow was also significantly lower in the type 1 diabetic patients than in the normal subjects. Heterogeneity of glucose uptake but not of blood flow was greater in the insulin-resistant type 1 diabetic patients both at rest (RD_g 31 ± 1 vs. 25 ± 2%, patients with type 1 diabetes vs. normal subjects, P < 0.05) and during exercise, compared with normal subjects (27 ± 1 vs. 21 ± 2%, respectively, P < 0.05). Exercise increased both glucose uptake and blood flow several-fold and significantly decreased both RD_g and RD_f. Heterogeneity of RD_g, was inversely associated with total glucose uptake (r = -0.54, P < 0.001, pooled data) and was highest in the most insulin-resistant patients. We concluded that both glucose uptake and blood flow are characterized by heterogeneity in human skeletal muscle, whose magnitude is inversely proportional to respective mean values. This implies that an increase in glucose uptake in human skeletal muscle is not a phenomenon, by which each unit increases its glucose uptake by a fixed amount but rather a spatially heterogeneous process.

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