https://scholars.lib.ntu.edu.tw/handle/123456789/494491
標題: | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation | 作者: | TIEN-JYUN CHANG Tseng H.-C. Liu M.-W. YI-CHENG CHANG Hsieh M.-L. LEE-MING CHUANG |
公開日期: | 2016 | 出版社: | Nature Publishing Group | 卷: | 6 | 起(迄)頁: | 23403 | 來源出版物: | Scientific Reports | 摘要: | Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whether metformin prevents MG-induced beta cell apoptosis is controversial. Here, we explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. MG treatment induced apoptosis of beta cells, impaired mitochondrial function, and prolonged activation of AMP-dependent protein kinase (AMPK). The MG-induced pro-apoptotic effects were abolished by an AMPK inhibitor. Pretreatment of GLP-1 reversed MG-induced apoptosis, and mitochondrial dysfunction, and suppressed prolonged AMPK activation. Pretreatment of GLP-1 reversed AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR)-induced apoptosis, and suppressed prolonged AMPK activation. However, metformin neither leads to beta cell apoptosis nor ameliorates MG-induced beta cell apoptosis. In parallel, GLP-1 also prevents MG-induced beta cell apoptosis through PKA and PI3K-dependent pathway. In conclusion, these data indicates GLP-1 but not metformin protects MG-induced beta cell apoptosis through improving mitochondrial function, and alleviating the prolonged AMPK activation. Whether adding GLP-1 to metformin provides better beta cell survival and delays disease progression remains to be validated. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961590088&doi=10.1038%2fsrep23403&partnerID=40&md5=ff5d9d4a63125b041d1d7124c8d20b0a https://scholars.lib.ntu.edu.tw/handle/123456789/494491 |
ISSN: | 2045-2322 | DOI: | 10.1038/srep23403 | SDG/關鍵字: | antidiabetic agent; cyclic AMP dependent protein kinase; glucagon like peptide 1; hydroxymethylglutaryl coenzyme A reductase kinase; metformin; methylglyoxal; phosphatidylinositol 3 kinase; animal; antagonists and inhibitors; apoptosis; cell survival; drug effects; metabolism; mitochondrion; pancreas islet beta cell; rat; signal transduction; tumor cell line; AMP-Activated Protein Kinases; Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Cyclic AMP-Dependent Protein Kinases; Glucagon-Like Peptide 1; Hypoglycemic Agents; Insulin-Secreting Cells; Metformin; Mitochondria; Phosphatidylinositol 3-Kinases; Pyruvaldehyde; Rats; Signal Transduction |
顯示於: | 醫學系 |
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