Protection of pancreatic β-cells against glucotoxicity by short-term treatment with GLP-1

Biochemical and Biophysical Research Communications
Sun-Hyun ParkDae-Kyu Song

Abstract

Glucagon-like peptide-1 (GLP-1) reduces pancreatic β-cell apoptosis in type 2 diabetes. Glucotoxiciy is a main cause of β-cell apoptosis in type 2 diabetes. The aims of this study were to investigate the anti-apoptotic mechanisms of GLP-1 against glucotoxicity and whether physiological short-term treatment with GLP-1 can protect β-cells from glucotoxicity-induced apoptosis. GLP-1 treatment for only 30 min alleviated high glucose-induced β-cell apoptosis. The effect of GLP-1 was related with phosphoinositide 3-kinase (PI3K)/AKT-S473 phosphorylation. The increase in pAKT-S473 led to suppression of FoxO-1. GLP-1-induced AKT-S473 activation and FoxO-1 suppression were abolished by the selective inactivation of mTOR complex (mTORC) 2 using small interfering RNA directed towards the rapamycin-insensitive companion of mTOR. The protective effect of GLP-1 on β-cell apoptosis was also abolished by the selective inactivation of mTORC2. Hence, the protective effect of GLP-1 against glucotoxicity may be mediated by FoxO-1 suppression through the PI3K/mTORC2/AKT-S473 phosphorylation. This report provides evidence that short-term treatment with GLP-1 is beneficial to protect against glucotoxicity-induced β-cell apoptosis.

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Citations

Apr 20, 2016·Frontiers in Pharmacology·Husnia I Marrif, Salma I Al-Sunousi
Sep 9, 2016·Applied Biochemistry and Biotechnology·Zaizhong NiMinggang Li
Jun 3, 2021·International Journal of Molecular Sciences·Safia CostesMagalie A Ravier

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