Insulin induces proliferation and cardiac differentiation of P 19 CL 6 cells in a dose‐dependent manner

• Published in: Development, growth & differentiation growth & differentiation, 2013-09, Vol.55 (7), p.676-686
• Main Authors: Li, Wen‐Yan, Song, Yang‐Liu, Xiong, Cheng‐Juan, Lu, Pei‐Qi, Xue, Li‐Xiang, Yao, Chun‐Xia, Wang, Wei‐Ping, Zhang, Shu‐Feng, Zhang, Shan‐Feng, Wei, Qing‐Xia, Zhang, Yan‐Yan, Zhao, Ji‐Min, Zang, Ming‐Xi
• Format: Article
• Language: English
• ISSN: 0012-1592; 1440-169X
• DOI: 10.1111/dgd.12075

Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of insulin in energy metabolism have been well studied, with most of the attention focused on glucose utilization, but the roles of insulin in cell proliferation and differentiation remain unclear. In this study, we observed for the first time that 10 nmol/L insulin treatment induces cell proliferation and cardiac differentiation of P 19 CL 6 cells, whereas 50 and 100 nmol/L insulin treatment induces P 19 CL 6 cell apoptosis and blocks cardiac differentiation of P 19 CL 6 cells. By using real‐time polymerase chain reaction ( PCR ) and W estern blotting analysis, we found that the m RNA levels of cyclin D 1 and α myosin heavy chain (α‐ MHC ) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100 nmol/L insulin treatment, whereas the m RNA levels of BCL‐2‐antagonist of cell death ( BAD ) exists a reverse trend. The similar results were observed in P 19 CL 6 cells expressing GATA ‐6 or peroxisome proliferator‐activated receptor α ( PPAR α). Our results identified the downstream targets of insulin, cyclin D 1, BAD , α‐ MHC , and GATA ‐4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.