INSULIN ATTENUATES INTRACELLULAR CALCIUM RESPONSES AND CELL CONTRACTION CAUSED BY VASOACTIVE AGENTS

In the present study, we examined the effects of insulin and insulin-l ike growth factor I (IGF-I) on cultured rat mesangial cell responses t o vasoactive agents. Intracellular calcium concentration (Ca2+i()) w as measured with the Fura-2 method in suspended mesangial cells. Pretr eatment of mesangial cells with insulin (from 0.05 to 5 mu g/ml) atten uated Ca2+ transients by platelet activating factor (PAF) in a dose de pendent and a time dependent manner. Insulin also attenuated sustained elevation of Ca2+(i) elicited by PAF. Basal Ca2+(i) was not affec ted by insulin pretreatment. Since the effective dose of insulin (0.5 mu g/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, insu lin pretreatment attenuated Ca2+(i) responses evoked by angiotensin II (Ang II) and endothelin-1. In addition, the pretreatment with insul in or IGF-I inhibited mesangial cell contraction in response to Ang II . The suppression of Ca2+(i) responses to vasoactive agents by insul in was abolished when extracellular Ca2+ was removed. These data sugge st that insulin, probably via IGF-I receptor, attenuates Ca2+(i) res ponses and cell contraction of mesangial cells induced by vasoactive a gents. It is likely that the change in Ca2+ influx from outside to ins ide the cell underlie the effect of insulin. The modification of mesan gial cell function through IGF-I receptor may play a role in the regul ation of glomerular hemodynamics.