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 dose-related manner. To explore the mechanism by which C-peptide exerts this insulinomimetic effect, here we report the effect of C-peptide on protein tyrosine phosphatase (PTP) activity and phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1). C-peptide inhibited PTP activity in a dose-dependent manner. A reverse bell-shaped dose-response curve was 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 stimulatory effect on glycogen synthesis. In association with the PTP inhibition by C-peptide, autophosphorylation of the insulin receptor and activation of IRS-1 were enhanced. These results suggest that C-peptide signal transduction may crosstalk with the insulin signaling pathway at the level of the insulin receptor.
Li
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ZG
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA.
Qiang
X
X
Sima
A A
AA
Grunberger
G
G
D000818:Animals; D002096:C-Peptide / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006003:Glycogen / Q000096:biosynthesis*; D055504:Insulin Receptor Substrate Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D020239:Receptor Cross-Talk; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D002096:C-Peptide; D004791:Enzyme Inhibitors; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D006003:Glycogen; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases