Insulin attenuates intracellular calcium responses and cell contraction caused by vasoactive agents.
In the present study, we examined the effects of insulin and insulin-like growth factor I (IGF-I) on cultured rat mesangial cell responses to vasoactive agents. Intracellular calcium concentration ([Ca2+]i) was measured with the Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with insulin (from 0.05 to 5 micrograms/ml) attenuated Ca2+ transients by platelet activating factor (PAF) in a dose dependent and a time dependent manner. Insulin also attenuated sustained elevation of [Ca2+]i elicited by PAF. Basal [Ca2+]i was not affected by insulin pretreatment. Since the effective dose of insulin (0.5 microgram/ml or higher) is much higher than the physiological concentration, the effects of insulin may be via IGF-I receptor. Indeed, IGF-I (50 ng/ml) similarly attenuated [Ca2+]i responses to PAF. Moreover, insulin pretreatment attenuated [Ca2+]i responses evoked by angiotensin II (Ang II) and endothelin-1. In addition, the pretreatment with insulin or IGF-I inhibited mesangial cell contraction in response to Ang II. The suppression of [Ca2+]i responses to vasoactive agents by insulin was abolished when extracellular Ca2+ was removed. These data suggest that insulin, probably via IGF-I receptor, attenuates [Ca2+]i responses and cell contraction of mesangial cells induced by vasoactive agents. It is likely that the change in Ca2+ influx from outside to inside the cell underlie the effect of insulin. The modification of mesangial cell function through IGF-I receptor may play a role in the regulation of glomerular hemodynamics.
Inishi
Y
Y
Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Okuda
T
T
Arakawa
T
T
Kurokawa
K
K
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D007328:Insulin; D010972:Platelet Activating Factor; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D002118:Calcium; D016257:Fura-2