详细记录  
题名:Toxicity generated through inhibition of pyruvate carboxylase and carnitine palmitoyl transferase-1 is similar to high glucose/palmitate-induced glucolipotoxicity in INS-1 beta cells.
作者:LEE JH; JUNG IR; CHOI SE; LEE SM; LEE SJ; HAN SJ; KIM HJ; KIM DJ; LEE KW; KANG Y;
来源:Mol Cell Endocrinol. 2013 Dec 11;383(1-2):48-59. doi: 10.1016/j.mce.2013.12.002. [ IF= 0.00 ] ]
URL :10.1016/j.mce.2013.12.002
日期:20140217
摘要:This work was initiated to determine whether toxicity generated through
inhibition of mitochondrial fuel metabolism is similar to high glucose/palmitate
(HG/PA)-induced glucolipotoxicity. Influx of glucose and free fatty acids into
the tricarboxylic acid (TCA) cycle was inhibited by treatment with the pyruvate
carboxylase (PC) inhibitor phenylacetic acid (PAA) and carnitine palmitoyl
transferase-1 (CPT-1) inhibitor etomoxir (Eto), or knockdown of PC and CPT-1.
Treatment of PAA/Eto or knockdown of PC/CPT-1 induced apoptotic death in INS-1
beta cells. Similar to HG/PA treatment, PAA/Eto increased endoplasmic reticulum
stress responses but decreased the Akt signal. JNK inhibitor or chemical
chaperone was protective against both PAA/Eto- and HG/PA-induced cell death. All
attempts to reduce [Ca2+]i, stimulate lipid metabolism, and increase the TCA
cycle intermediate pool protected PAA/Eto-induced death as well as HG/PA-induced
death. These data suggest that signals induced from impaired mitochondrial fuel
metabolism play a critical role in HG/PA-induced glucolipotoxicity.

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