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

• DOI: 10.1016/j.bbrc.2015.02.139
• Publication Date: 2015-03-07T02:48:45Z
• Authors: Sun-Hyun Park; Jae-Hyung Park; Hye-Min Shim; Ann-Yae Na; Ki-Churl Bae; Jeung-Geun Lim; Dae-Kyu Song
• Keywords: 0301 basic medicine; Base Sequence; TOR Serine-Threonine Kinases; 610; Mechanistic Target of Rapamycin Complex 2; Real-Time Polymerase Chain Reaction; 3. Good health; Mice, Inbred C57BL; Islets of Langerhans; Mice; 03 medical and health sciences; Glucose; Glucagon-Like Peptide 1; Multiprotein Complexes; Animals; Phosphorylation; DNA Primers

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.