Glucagon-like peptide-1 analog-mediated protection against cholesterol-induced apoptosis via mammalian target of rapamycin activation in pancreatic βTC-6 cells -1mTORβTC-6.

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.