The importance of transcapillary insulin delivery as a regulated step was explored in an insulin resistant rat model. Oophorectomized female rats were exposed to testosterone (OVX + T) for 8 weeks and examined with insulin clamps, muscle microdialysis, and analyses of insulin distribution kinetics. The results were compared with those obtained in sham-operated control rats. After OVX + T, onset of glucose uptake in skeletal muscle was significantly (P < 0.001–0.05) delayed compared with controls as measured by the glucose infusion rate (GIR) during a euglycaemic, hyperinsulinaemic clamp (5 mU kg–1 min–1). The increase in interstitial insulin concentrations was also significantly (P < 0.05) delayed (15–20% lower) in OVX + T treated rats compared with control rats, but to such a small magnitude that this alone could not explain the late onset of the insulin effect. Skeletal muscle capillary density, examined histochemically, was diminished (P < 0.01–0.001) by 20–25% after treatment with OVX + T compared with control animals, as was the peripheral blood flow (P < 0.05) by 40–45%, measured with the microsphere technique. Insulin binding was reduced in proportion to the reduced (P < 0.01) vascular surface area by OVX + T treatment. Transcapillary transport rate of insulin, measured by comparisons of the kinetics of inulin and insulin spaces in muscle with time, tended (ns) to be lower after OVX + T compared with control rats (30–40%) as a reflection of the lower capillary surface area. The data suggest that the delayed onset of insulin action after OVX + T results from combined defects in the muscle cell at a postreceptor level and, to a lesser extent, from retarded transcapillary delivery of insulin.
No Supplementary Data
Document Type: Research Article
Department of Heart and Lung Diseases and the Wallenberg Laboratory, Göteborg, Sweden
Department of Nephrology, University of Lund, Lund, Sweden
Department of Internal Medicine and the Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Sweden
Publication date: 2001-04-01