title: Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner.
abstract: 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 P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells. By using real-time polymerase chain reaction (PCR) and Western blotting analysis, we found that the mRNA levels of cyclin D1 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 mRNA levels of BCL-2-antagonist of cell death (BAD) exists a reverse trend. The similar results were observed in P19CL6 cells expressing GATA-6 or peroxisome proliferator-activated receptor α (PPARα). Our results identified the downstream targets of insulin, cyclin D1, BAD, α-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Li
authors.forename: Yang-Liu
authors.initials: YL
authors.lastname: Song
authors.forename: Cheng-Juan
authors.initials: CJ
authors.lastname: Xiong
authors.forename: Pei-Qi
authors.initials: PQ
authors.lastname: Lu
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Xue
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yao
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Shan-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Wei
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhao
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494820:Bad protein, mouse; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D007328:Insulin; C584019:Myh6 protein, mouse; D047493:PPAR alpha; D051025:bcl-Associated Death Protein; D019938:Cyclin D1; D018995:Myosin Heavy Chains
keywords: BCL-2-antagonist of cell death; cell differentiation; cell growth; cyclin D1; insulin