Insulin regulates glucagon-like peptide-1 secretion by pancreatic alpha cells
Insulin regulates glucagon-like peptide-1 secretion by pancreatic alpha cells
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胰岛素调节胰腺α细胞分泌胰高血糖素样肽-1
DOI：
10.1007/s12020-018-1684-3
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发表时间：
2018-11-01
期刊：
影响因子：
3.7
通讯作者：
Chen, Li
中科院分区：
文献类型：
--
作者：
Liu, Pan;Song, Jia;Chen, Li
目的胰高血糖素原在胰腺α细胞和肠上皮L细胞中均有表达，并被不同的激素原转化酶（PCs）裂解为胰高血糖素和胰高血糖素样肽-1 （GLP-1）。最近的研究表明-细胞也可以分泌GLP-1，这可能改善胰岛功能。然而，影响细胞分泌GLP-1的因素知之甚少。在这项研究中，我们研究了胰岛素是否促进细胞分泌GLP-1，以及这一现象的机制。方法将α细胞株in - r1 - g9分别培养于低糖和高糖培养基中，观察葡萄糖浓度对胰岛素作用的影响。我们还用不同时间和不同剂量的胰岛素治疗In-R1-G9细胞。测定GLP-1和胰高血糖素蛋白的表达水平。此外，我们还评估了ERK和磷脂酰肌醇-3-激酶/AKT （PI3K/AKT）通路活性水平和激素原转化酶表达水平，以阐明胰岛素影响GLP-1细胞分泌的机制。结果胰岛素在高糖条件下促进GLP-1分泌具有时间和剂量依赖性。与胰岛素处理的细胞相比，LY294002抑制PI3K/AKT通路和PD98059抑制Ras/丝裂原活化蛋白激酶（Ras/ MAPK）通路分别减少了抑制剂处理的细胞中GLP-1的分泌。胰岛素使相应组in - r1 - g9细胞中激素原转换酶1/3的表达水平较对照组升高。结论高糖条件下胰岛素通过诱导PC1/3表达促进胰腺α细胞分泌GLP-1，这一现象可能主要与PI3K/AKT通路激活有关。
PurposeProglucagon is expressed in both pancreatic alpha cells and intestinal epithelial L cells and is cleaved into glucagon and glucagon-like peptide-1 (GLP-1) by different prohormone convertases (PCs). Recent studies have shown that -cells can also secrete GLP-1, which may improve islet function. However, little is known about the factors influencing GLP-1 secretion by cells. In this study, we investigated whether insulin promotes GLP-1 secretion by cells, as well as the mechanisms underlying this phenomenon.MethodsWe cultured the alpha-cell line In-R1-G9 in low- or high-glucose medium in the presence or absence of insulin to determine the influence of glucose concentrations on the actions of insulin. We also treated In-R1-G9 cells with insulin for different times and at different doses. Then GLP-1 and glucagon protein expression levels were estimated. Moreover, ERK and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathway activity levels and prohormone convertase expression levels were evaluated to elucidate the mechanism underlying the effects of insulin on GLP-1 secretion by -cells.ResultsInsulin promoted GLP-1 secretion in a time- and dose-dependent manner under high-glucose conditions. Inhibiting the PI3K/AKT pathway with LY294002 and the Ras/mitogen-activated protein kinase (RAS/MAPK) pathway with PD98059 reduced GLP-1 secretion, respectively, in inhibitor-treated cells compared with insulin-treated cells. Moreover, insulin increased prohormone convertase 1/3 expression levels in the corresponding group of IN-R1-G9 cells compared with the control group of cells.ConclusionInsulin facilitates GLP-1 secretion by pancreatic alpha cells by inducing PC1/3 expression under high-glucose conditions, a phenomenon that may be associated mainly with PI3K/AKT pathway activation.