Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt Pathway In vitro and In vivo

二甲双胍 内科学 内分泌学 胰岛素 蛋白激酶B 胰岛素抵抗 体内 胰岛 糖尿病 医学 生物 小岛 信号转导 细胞生物学 生物技术
作者
Jianting Li,Qiang Jiang,Xin Wang,Lulu Hou,Lulu Wang,Kai Lou,Shuguang Pang
出处
期刊:Combinatorial Chemistry & High Throughput Screening [Bentham Science]
卷期号:27 (18): 2691-2698
标识
DOI:10.2174/0113862073246747230920170201
摘要

In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet β-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic β-cells.Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic βcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention.The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells.High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets.Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.
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