Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells.
Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells.
复制标题
DOI：
10.1371/journal.pone.0097868
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Csala M
中科院分区：
文献类型：
--
作者：
Simon-Szabó L;Kokas M;Mandl J;Kéri G;Csala M
Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid levels playing a central role in the development and progression of obesity related diseases. Saturated fatty acids cause insulin resistance and reduce insulin production in the pancreatic islets, thereby generating a vicious cycle, which potentially culminates in type 2 diabetes. The underlying endoplasmic reticulum (ER) stress response can lead to even β-cell death (lipoapoptosis). Since improvement of β-cell viability is a promising anti-diabetic strategy, the protective effect of metformin, a known insulin sensitizer was studied in rat insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells. Attenuation of β-cell lipotoxicity was also revealed by lower induction/activation of various ER stress markers, e.g. phosphorylation of eukaryotic initiation factor 2α (eIF2α), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer binding protein homologous protein (CHOP). Our results indicate that the β-cell protective activity of metformin in lipotoxicity can be at least partly attributed to suppression of ER stress.
登录
查看更多内容
影响因子：
7.2
作者：
Beeharry, N;Chambers, JA;Green, IC
通讯作者：
Green, IC
影响因子：
3.9
作者：
Cnop, Miriam;Igoillo-Esteve, Mariana;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
影响因子：
7.7
作者：
Accili, D
通讯作者：
Accili, D
影响因子：
7.7
作者：
Musi, N;Hirshman, MF;Goodyear, LJ
通讯作者：
Goodyear, LJ
影响因子：
3.3
作者：
Fu, Zhuo;Gilbert, Elizabeth R.;Liu, Dongmin
通讯作者：
Liu, Dongmin