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Direct Measurements of the Permeability Surface Area for Insulin and Glucose in Human Skeletal Muscle

Lundberg Laboratory for Diabetes Research (S.G., M.S., L.S., P.L.), Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden; and Department of Clinical Physiology (J.W.), Karolinska Hospital, S-17176 Stockholm, Sweden

Address all correspondence and requests for reprints to: Soffia Gudbjörnsdóttir, Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: soffia. gudbjornsdottir{at}medic.gu.se.

To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle.

Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp.

PS for glucose increased significantly from 0.29 ± 0.1 to 0.64 ± 0.2 ml/min·100 g after oral glucose tolerance test, and glucose uptake increased from 1.2 ± 0.4 to 2.6 ± 0.6 µmol/min·100 g (P < 0.05). During one-step hyperinsulinemic clamp (plasma insulin, 1.962 pmol/liter), PS for glucose increased from 0.2 ± 0.1 to 2.3 ± 0.9 ml/min·100 g (P < 0.05), and glucose uptake increased from 0.6 ± 0.2 to 5.0 ± 1.4 µmol/min·100 g (P < 0.05). During the two-step clamp (plasma insulin, 1380 ± 408 and 3846 ± 348 pmol/liter), the arterial-interstitial difference and PS for insulin were constant. The PS for glucose tended to increase (P = not significant), whereas skeletal muscle blood flow increased from 4.4 ± 0.7 to 6.2 ± 0.8 ml/min·100 ml (P < 0.05).

The present data show that PS for glucose is markedly increased by oral glucose, whereas a further vasodilation exerted by high insulin concentrations may not be physiologically relevant for capillary delivery of either glucose or insulin in resting muscle.

This work was supported by grants from the Swedish Research Council (project no. 10864, 11330, and 12206), the Swedish Diabetes Association, the Novo Nordisk Foundation, the Inga-Britt and Arne Lundbergs Foundation, the Knut och Alice Wallenberg Foundation, and the Magnus Bergvalls Foundation.

Abbreviations: AI, Arterial-interstitial; BMI, body mass index; GIR, glucose infusion rate; ns, not significant; OGTT, oral glucose tolerance test; PS, permeability surface.

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