Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes – Role of insulin and IGF-I receptors

► In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors were detected. ► Insulin and IGF-I activate their cognate receptors and IGF-I also hybrid receptors. ► IGF-II activates IR, IGF-IR and insulin/IGF-I hybrid receptors. ► Insulin and IGF-I are partial agonists to each other's receptors. We compared insulin and IGF effects in adipocytes expressing IR (insulin receptors), and preadipocytes expressing IR and IGF-IR (IGF-I receptors). Treatment of adipocytes with insulin, IGF-II or IGF-I resulted in phosphorylation of IR. Order of potency was insulin>IGF-II>IGF-I. In preadipocytes IR, IGF-IR and insulin/IGF-I hybrid receptors (HR) were detected. Treatment of preadipocytes with IGF-I and IGF-II 10−8M resulted in activation of IGF-IR and IR whereas insulin was more potent in activating IR, with no effect on IGF-IR. In adipocytes glucose transport was 100-fold more sensitive to insulin than to IGFs and the maximal effect was higher with insulin. In preadipocytes glucose accumulation and DNA synthesis was equally sensitive to insulin and IGFs but the maximal effect was higher with IGF-I. In conclusion, insulin and IGF-I activate their cognate receptors and IGF-I also HR. IGF-II activates IR, IGF-IR and HR. Insulin and IGF-I are partial agonists to each other's receptors.