Glucagon‐like peptide‐1 analog‐mediated protection against cholesterol‐induced apoptosis via mammalian target of rapamycin activation in pancreatic βTC‐6 cells 胰高血糖素样多肽‐1类似物激活mTOR通路减轻胆固醇诱导的βTC‐6细胞凋亡

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Abstract
Background: Glucagon‐like peptide‐1 (GLP‐1) has been shown to protect pancreatic β‐cells against glucolipotoxicity via activation of the Akt pathway. The present study investigated the protective effects of the GLP‐1 analog liraglutide against cholesterol‐induced lipotoxicity and the mechanisms involved.Methods: The mouse βTC‐6 pancreatic β‐cell line was preincubated for 30 min with 10 nmol/L liraglutide alone or in combination with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (1 μmol/L) before being exposed to 5 mmol/L cholesterol for 6 h. 4′,6′‐Diamidino‐2‐phenylindole (DAPI) staining and Western blot analyses were used to assess the effects of liraglutide on cholesterol‐induced apoptosis and the phosphorylation of Akt and mTOR.Results: Cholesterol significantly promoted cell apoptosis and attenuated the phosphorylation of Akt and mTOR, effects that were significantly reversed by liraglutide. Furthermore, rapamycin pretreatment alone significantly increased cholesterol‐induced apoptosis compared with cholesterol‐treated cells without any other pretreatment.Conclusions: The data indicate that mTOR signaling is an essential mediator in the protection of pancreatic β‐cells against cholesterol‐induced apoptosis by a GLP‐1 analog.
Funding Information
  • Zhejiang Provincial Natural Science Foundation of China (Y2100140)
  • Health Bureau of Zhejiang Province (2010KYA108)

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