C-peptide attenuates protein tyrosine phosphatase activity and enhances glycogen synthesis in L6 myoblasts

Recent studies suggest that C-peptide might play a role in a broad range of biological activities. We have provided evidence that C-peptide stimulates glycogen synthesis in insulin-responsive rat skeletal muscle cells in a do se-related manner. To explore the mechanism by which C-peptide exerts this insulinomimetic effect, here we report the effect of C-peptide on protein t yrosine phosphatase (PTP) activity and phosphorylation of the insulin recep tor and insulin receptor substrate-1 (IRS-1). C-peptide inhibited PTP activ ity in a dose-dependent manner. A reverse bell-shaped dose-response curve w as shown with the maximum inhibition of PTP activity at a concentration of 3 nM of C-peptide, which is the same concentration achieving the maximum st imulatory effect on glycogen synthesis. In association with the PTP inhibit ion by C-peptide, autophosphorylation of the insulin receptor and activatio n of IRS-1 were enhanced. These results suggest that C-peptide signal trans duction may crosstalk with the insulin signaling pathway at the level of th e insulin receptor. (C) 2001 Academic Press.