title: Protection of pancreatic β-cells against glucotoxicity by short-term treatment with GLP-1.
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.
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Sun-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Shim
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ann-Yae
authors.initials: AY
authors.lastname: Na
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ki-Churl
authors.initials: KC
authors.lastname: Bae
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jeung-Geun
authors.initials: JG
authors.lastname: Lim
authors.affiliation: Department of Physiology & Obesity-mediated Disease Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea. Electronic address: dksong@kmu.ac.kr.
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects*; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D046912:Multiprotein Complexes; D052216:Glucagon-Like Peptide 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: FoxO-1; Glucagon-like peptide-1; Glucotoxiciy; Pancreatic β-cell; Type 2 diabetes; mTOR complex 2