Insulin insensitivity and delayed transcapillary delivery of insulin in oophorectomized rats treated with testosterone
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.
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