EXTRACELLULAR DISTRIBUTION OF INSULIN IN MUSCLE OF RATS EXPOSED TO LONG-TERM HYPERINSULINEMIA

The importance oi increased capillary density for the regulation of in sulin sensitivity by transcapillary delivery of insulin to muse e cell s in insulin-exposed rats was investigated by direct microdialysis mea surements of interstitial [(125)]insulin concentrations in the femoral muscle during an euglycaemic hyperinsulinaemic clamp. In insulin-expo sed rats plasma insulin was similar to 25% (P < 0.05) higher than that in control animals during the first 100 min and reached their maximal concentrations after 100 min. After a nitroprusside infusion given at 100 min both groups had similar concentrations of insulin in plasma a s well as in muse e interstitial fluid. However, mean glucose infusion rare during the first clamp hour was 20.5+/-2.3 and 12.6+/-5.2 mg kg( -1) min(-1) (P < 0.05) in insulin-exposed and control animals. respect ively. During the second clamp hour the corresponding figures were 21. 1+/-2.4 and 13.9+/-2.6 (P < 0.05). It may be concluded that capillariz ation and/or nitroprusside affected plasma insulin concentrations with out altering either the interstitial insulin levels or the insulin eff ect on glucose consumption. The data suggest that the elevated insulin sensitivity after chronic insulin exposure is dependent on other than transcapillary transport events and demonstrate the different kinetic s for insulin distribution in plasma and in the interstitial fluid.