TITLE:
Autophagy induced by glibenclamide serves as a defense against apoptosis in INS-1 rat insulinoma cells
AUTHORS:
Hua Su, Xingyan Liu, Ling Su, Li Zhang, Xiangguo Liu, Hong Ji, Haiqin Rong
KEYWORDS:
Glibenclamide; Pancreatic Beta-Cell; Autophagy; Apoptosis; p70 S6K
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.3 No.3,
July
22,
2013
ABSTRACT: Glibenclamide, a
blocker of ATP-sensitive potassium channels, has been found to induce apoptosis
in some cell types, including pancreatic beta-cells. Since autophagy plays doubleedged roles in pancreatic beta-cell survival, frequently through cross-talking
with apoptosis, we investigated if glibenclamide induced autophagy in INS-1 rat
insulinoma cells and the influence of autophagy on apoptosis. Mammalian target
of rapamycin (mTOR) is a negative regulator of autophagy. As one of the
substrates of mTOR, p70 S6 kinase (p70 S6K) is phosphorylated upon mTOR
activation. Our results showed that glibenclamide induced an elevated protein
level of the autophagy marker LC3-II, while decreasing phosphorylated p70 S6K, indicative
of inhibition on mTOR signaling in INS-1 cells. Furthermore, inhibiting glibenclamide-induced
autophagy via knocking down the autophagy essential gene Atg7 decreased cell viability and
increased apoptosis in INS-1 cells. Our results indicate that glibenclamide
induces autophagy in INS-1 cells, and that autophagy activation is exerting a
protective activity against apoptosis.