Activation of IRS-2-mediated signal transduction by IGF-1 but not TGF-αor EGF, augments pancreatic β-cell proliferation

摘要

Transforming growth factor(TGF)-α-and epidermal growth factor(EGF)-induced signal transduction was directly compared with that of glucose and insulin-like growth factor-1(IGF-1)in cells. TGF-α/EGF tran- lular-regulated kinase(Erk)-1/2(> 20-fold), glycogen synthase kinase(GSK)-3(>10-fold), and protein kinase B(PKB)(Ser~473 and Thr~308), but did not increase [~3H]thymidine incorporation. In contrast, phosphoryla- tion of Erk 1/2, GSK-3, and PKB in response to glucose and IGF-1 was more prolonged(> 24 h)and, though not as robutst as TGF-α/EGF, did increaseβ-cell prolifera- tion.