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学科主题: 基础医学
题名:
alpha-lipoic acid inhibits high glucose-induced apoptosis in HIT-T15 cells
作者: Yang, Yi1,2; Wang, Weiping1; Liu, Yinan1; Guo, Ting1; Chen, Ping1; Ma, Kangtao1; Zhou, Chunyan1
关键词: alpha-lipoic acid ; apoptosis ; diabetes ; islet beta cells ; Pdx1
刊名: DEVELOPMENT GROWTH & DIFFERENTIATION
发表日期: 2012-06-01
DOI: 10.1111/j.1440-169X.2012.01356.x
卷: 54, 期:5, 页:557-565
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Developmental Biology
研究领域[WOS]: Cell Biology ; Developmental Biology
关键词[WOS]: INSULIN-SECRETION ; MITOCHONDRIAL DYSFUNCTION ; OXIDATIVE STRESS ; SKELETAL-MUSCLE ; PROTEIN-KINASE ; BETA-CELLS ; PDX1 ; AKT ; INVOLVEMENT ; EXPRESSION
英文摘要:

High blood glucose plays an important role in the pathogenesis of diabetes. alpha-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 alpha-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.

语种: 英语
所属项目编号: 30470402 ; 81071675 ; 81170713 ; 81160103 ; 20070001798 ; 20060001107 ; NXIC2011010 ; NZ1097
项目资助者: National Natural Science Foundation of China ; Specialized Research Fund for the New Teacher in Doctoral Program of Higher Education ; Specialized Research Fund for the Doctoral Program of Higher Education ; Science Research and International Cooperation Project of Ningxia Hui Autonomous Region ; National Natural Science Foundation of Ningxia
WOS记录号: WOS:000305188300003
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51323
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Ningxia Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Yinchuan 750004, Ningxia Hui Aut, Peoples R China

Recommended Citation:
Yang, Yi,Wang, Weiping,Liu, Yinan,et al. alpha-lipoic acid inhibits high glucose-induced apoptosis in HIT-T15 cells[J]. DEVELOPMENT GROWTH & DIFFERENTIATION,2012,54(5):557-565.
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