摘要
目的:探讨慢性高糖状态下NIT-1细胞乳酸脱氢酶-A(LDH—A)活性与胰岛素分泌的关系。方法:以高糖单独或与草氨酸钠(LDH-A竞争性抑制剂)、N-乙酰半胱氨酸(NAC)联合作用于NIT-1细胞,测定LDH-A表达与活性、乳酸、反应氧族(ROS)和胰岛素分泌的相关性。结果:慢性高糖作用可提高NIT-1细胞LDH-A表达与活性、乳酸水平,使胰岛素分泌受损;草氨酸钠作用可降低慢性高糖诱导的NIT-1细胞LDH-A活性和促进乳酸水平增高,改善细胞胰岛素分泌;此外,NAC作用引起的NIT-1细胞ROS水平下降伴随LDH-A活性、乳酸水平下降和胰岛素分泌改善。结论:慢性高糖诱导的LDH—A活性增高引起NIT-1细胞胰岛素分泌缺陷;ROS激活LDH—A可能是胰岛D细胞葡萄糖毒性的机制之一。
Objective: To investigate the relationship between lactate dehydrogenase-A (LDH-A) activity and insulin secretion under chronic high-glucose conditions in NIT-1 cells. Methods: NIT-1 cells were treated with high glucose in presence/absence of oxamate (a competitive inhibitor of LDH-A) or N-acetylcysteine (NAC), LDH-A expression, activity, lactate production, reactive oxygen species (ROS), and insulin secretion were examined. Results: Chronically high glucose levels enhanced LDH-A expression, activity, and lactate production, and impaired insulin secretion in NIT-1 cells. Treatment with oxamate diminished the elevation of LDH-A activity induced by high glucose levels, reduced lactate production, and im- proved the impaired insulin secretion from NIT-1 cells observed in the absence of inhibitor. In addition, the reduction in ROS levels by NAC occurred simultaneously with the inhibition of LDH-A activity, lactate production, and the improvement in insulin secretion of NIT-1 cells. Conclusion: The results of our study indicate that increased LDH-A activity induced by chronic exposure to high glucose contributes to insulin secretory defect in NIT-1 cells. LDH-A activated by ROS may be one of the mechanisms of beta-cell glucotoxicity.
出处
《按摩与康复医学》
2014年第6期230-233,共4页
Chinese Manipulation and Rehabilitation Medicine
基金
广东省药学会基金资助项目,编号:H002012005
关键词
胰岛β细胞
乳酸脱氢酶-A
胰岛素分泌
反应氧族
葡萄糖毒性
Pancreatic beta-cell
lactate dehydrogenase-A
insulin secretion
reactive oxygen species
glucotoxicity