Exendin-4 promotes pancreatic β-cell proliferation via inhibiting the expression of Wnt5a

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• 作者：Xinger Wu ; Weiwei Liang ; Hongyu Guan ; Juan Liu ; Liehua Liu ; Hai Li…
• 关键词：Exendin ; 4 ; Pancreatic β cell ; Proliferation ; Wnt5a ; CaMKII
• 刊名：Endocrine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：55
• 期：2
• 页码：398-409
• 全文大小：
• 刊物主题：Endocrinology; Diabetes; Internal Medicine; Science, Humanities and Social Sciences, multidisciplinary;
• 出版者：Springer US
• ISSN：1559-0100
• 卷排序：55

文摘

Exendin-4, a glucagon-like peptide-1 receptor agonist, is currently regarded as an effective therapeutic strategy for type-2 diabetes. Previous studies indicated that exendin-4 promoted β cell proliferation. However, the underlying mechanisms remain largely unknown. Recently it was reported that exendin-4 promoted pancreatic β cell proliferation by regulating the expression level of Wnt4. The present study was designed to investigate whether other Wnt isoforms take part in accommodation of β-cell proliferation. We found that exendin-4 promotes the proliferation and suppresses the expression of Wnt5a in INS-1 cell line and C57Bl/6 mouse pancreatic β-cells. Further mechanistic study demonstrated that exendin-4 promoted INS-1 cell proliferation partly through down-regulating the expression of Wnt5a. Furthermore, Wnt5a could induce the activation of calmodulin-dependent protein kinase II in INS-1 cells, thereby decreasing the cellular stable β-catenin and its nuclear translocation, and finally reduce the expression of cyclin D1. In addition, we also found that both of the receptors (Frz-2 and Ror-2) mediated the effect of Wnt5a on β cell line INS-1 proliferation. Taken together, this study suggests that Wnt5a plays a critical role in exendin-4-induced β-cell proliferation, indicating that Wnt5a might be a novel regulator in counterbalance of β cell mass.