title: α-lipoic acid inhibits high glucose-induced apoptosis in HIT-T15 cells.
abstract: High blood glucose plays an important role in the pathogenesis of diabetes. α-lipoic acid (LA) has been used to prevent and treat diabetes, and is thought to act by increasing insulin sensitivity in many tissues. However, whether LA also has a cytoprotective effect on pancreatic islet beta cells remains unclear. In this study, we assessed whether LA could inhibit apoptosis in beta cells exposed to high glucose concentrations. HIT-T15 pancreatic beta cells were treated with 30 mmol/L glucose in the presence or absence of 0.5 mmol/L LA for 8 days. LA significantly reduced the numbers of apoptotic HIT-T15 cells and inhibited the cell overgrowth normally induced by high glucose treatment. Additionally, LA inhibited insulin expression and secretion in HIT-T15 cells induced by high glucose. Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene expression, reduced Bax gene expression, and promoted phosphorylation of Akt in HIT-T15 cells treated with high glucose. Intriguingly, knockdown of Pdx1 expression partially offset the anti-apoptotic effect of LA. However, inhibition of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05). Moreover, LA only slightly attenuated reactive oxygen species (ROS) production and augmented mitochondrial membrane potential. Therefore, our data suggest that α-lipoic acid can effectively attenuate high glucose-induced HIT-T15 cell apoptosis probably by increasing Pdx1 expression. These findings provide a new interpretation on the role of LA in the treatment of diabetes.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D006224:Cricetinae; D019610:Cytoprotection / Q000187:drug effects; D003920:Diabetes Mellitus / Q000209:etiology; D005947:Glucose / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
chemical_list: D002867:Chromones; D018398:Homeodomain Proteins; D007328:Insulin; D009025:Morpholines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C084010:pancreatic and duodenal homeobox 1 protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008063:Thioctic Acid; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose