Rapid formation of capillary endothelial cells in rat skeletal muscle after exposure to insulin.
Research has suggested a role for insulin delivery through capillaries in muscle in the regulation of insulin sensitivity. Therefore, the formation and turn-over of capillary endothelial cells in muscle were studied in relation to exposure to moderately elevated insulin concentrations with or without concomitant increase of corticosterone concentrations. Female rats were exposed to a moderate, physiological hyperinsulinaemia (approximately 450 pmol/l) for 24 h 48 h, 3 days, 7 days and 7 weeks. 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 corticosterone secretion intact. Rats were exposed to insulin with controlled, non-elevated corticosterone concentrations after adrenalectomy and corticosterone substitution; compared to controls, the number of mitoses in capillary endothelial cells in the soleus and extensor digitorum longus muscle were approximately doubled after 24 h, reaching a maximum, about fivefold higher than controls, after 3 days. After 7 weeks of insulin exposure there were no longer any significant differences between control and insulin-exposed rats. The number of capillaries per unit muscle surface area was moderately (10-15%) but significantly increased at 7 days (only the extensor digitorum longus muscle) and 7 weeks (the extensor digitorum longus and the soleus muscles). In rats exposed to insulin, with intact adrenals, endogenous corticosterone production resulted in concentrations about threefold higher than in rats adrenalectomized with subsequent corticosterone substitution. In these rats the increase in mitoses in capillary endothelium was totally abolished. The results of this study suggest that exposure to insulin in this rat model is followed by a dramatic short-term increase in the formation of new capillary endothelial cells in muscle. It is also suggested that this growth factor-like effect of insulin is abolished by corticosterone. It is suggested that insulin and corticosterone exert opposite effects on the capillary network in muscles, which might be important for the insulin supply to this tissue, and hence for regulation of insulin sensitivity.
Holmäng
A
A
Wallenberg Laboratory, Department of Heart and Lung Diseases, Sahlgrenska University Hospital, Göteborg, Sweden.
Jennische
E
E
Björntorp
P
P
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006946:Hyperinsulinism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D011433:Propranolol; D003345:Corticosterone