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.