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Decreased Muscle Capillary Permeability Surface Area in Type 2 Diabetic Subjects

Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, S-413 45 Göteborg, 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.

Capillary recruitment in muscles, induced by insulin, has been proposed to be impaired in insulin-resistant states. To elucidate the mechanisms regulating capillary transport of insulin and glucose in type 2 diabetes, we directly calculated the permeability-surface area product (PS) for glucose and insulin in muscle.

Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in type 2 diabetic male subjects and age- and weight-matched controls during a euglycemic-hyperinsulinemic clamp.

During steady-state hyperinsulinemia, arterial plasma glucose was 5.8 ± 0.1 and 5.9 ± 0.1 mmol/liter [not significant (NS)] in the obese and type 2 diabetic subjects, respectively. Venous glucose was significantly lower in the obese group compared with the type 2 diabetic subjects, 4.3 ± 02 vs. 4.9 ± 0.2 mmol/liter (P < 0.05). Arterial insulin was 1494 ± 90 and 1458 ± 132 pmol/liter (NS) in the obese and type 2 diabetic subjects, respectively.

The glucose infusion rate during steady-state hyperinsulinemia was 10.8 ± 0.8 and 7.2 ± 0.4 mg/kg·min in the obese and diabetic subjects, respectively (P < 0.01). Interstitial-arterial lactate difference was significantly higher in the obese subjects.

During steady-state hyperinsulinemia, PS for glucose was significantly higher in the obese subjects (1.1 ± 0.2 vs. 0.5 ± 0.1 ml/min·100 g, P < 0.05). Glucose uptake was also significantly higher in the obese subjects (3.0 ± 0.4 vs. 1.8 ± 0.3 µmol/min·100 g, P < 0.05). During steady-state hyperinsulinemia, PS for insulin was 0.4 ± 0.1 and 0.3 ± 0.1 ml/min·100 g in the obese and diabetic subjects, respectively (NS), and insulin uptake was 258 ± 54 vs. 168 ± 24, respectively (NS). When both subject groups were pooled together, a significant correlation was found between PS for glucose and glucose uptake during steady-state hyperinsulinemia. Skeletal muscle blood flow during steady-state hyperinsulinemia was 1.9 ± 0.2 and 2.3 ± 0.4 ml/100 g·min in the obese and diabetic subjects, respectively (NS). Blood flow did not increase during hyperinsulinemia in either of the two groups.

The present data clearly show that PS for glucose is subnormal during steady-state hyperinsulinemia in insulin-resistant type 2 diabetic subjects. Furthermore, there was a close correlation between glucose uptake and PS for glucose but not between blood flow and PS. We suggest that PS is a more sensitive marker for insulin resistance during hyperinsulinemia than limb flow. The lower capacity for transcapillary passage found in the type 2 diabetic subjects is suggested to further aggravate insulin resistance.

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