RAPID FORMATION OF CAPILLARY ENDOTHELIAL-CELLS IN RAT SKELETAL-MUSCLEAFTER EXPOSURE TO INSULIN

Research has suggested a role for insulin delivery through capillaries in muscle in the regulation of insulin sensitivity. Therefore, the fo rmation and turn-over of capillary endothelial cells in muscle were st udied in relation to exposure to moderately elevated insulin concentra tions with or without concomitant increase of corticosterone concentra tions. Female rats were exposed to a moderate, physiological hyperinsu linaemia (similar to 450 pmol/l) for 24 h 48 h, 3 days, 7 days and 7 w eeks. Propranolol was used to inhibit elevated adrenergic activity. In one insulin-exposed group, corticosterone secretion was controlled by adrenalectomy with substitution of corticosterone to maintain normal concentrations, while another group was left with adrenal corticostero ne secretion intact. Rats were exposed to insulin with controlled, non -elevated corticosterone concentrations after adrenalectomy and cortic osterone substitution; compared to controls, the number of mitoses in capillary endothelial cells in the soleus and extensor digitorum longu s muscle were approximately doubled after 24 h, reaching a maximum, ab out fivefold higher than controls, after 3 days. After 7 weeks of insu lin exposure there were no longer any significant differences between control and insulin-exposed rats. The number of capillaries per unit m uscle surface area was moderately (10-15%) but significantly increased at 7 days (only the extensor digitorum longus muscle) and 7 weeks (th e extensor digitorum longus and the soleus muscles). In rats exposed t o insulin, with intact adrenals, endogenous corticosterone production resulted in concentrations about threefold higher than in rats adrenal ectomized with subsequent corticosterone substitution. In these rats t he increase in mitoses in capillary endothelium was totally abolished. The results of this study suggest that exposure to insulin in this ra t model is followed by a dramatic short-term increase in the formation of new capillary endothelial cells in muscle. It is also suggested th at this growth factor-like effect of insulin is abolished by corticost erone. It is suggested that insulin and corticosterone exert apposite effects on the capillary network in muscles, which might be important for the insulin supply to this tissue, and hence for regulation of ins ulin sensitivity.