CAJ | 학술논문

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β细胞葡萄糖毒性的机制之一。
목적：탐토만성고당상태하NIT-1세포유산탈경매-A（LDH-A）활성여이도소분비적관계。방법：이고당단독혹여초안산납（LDH-A경쟁성억제제）、N-을선반광안산（NAC）연합작용우NIT-1세포，측정LDH-A표체여활성、유산、반응양족（ROS）화이도소분비적상관성。결과：만성고당작용가제고NIT-1세포LDH-A표체여활성、유산수평，사이도소분비수손；초안산납작용가강저만성고당유도적NIT-1세포LDH-A활성화촉진유산수평증고，개선세포이도소분비；차외，NAC작용인기적NIT-1세포ROS수평하강반수LDH-A활성、유산수평하강화이도소분비개선。결론：만성고당유도적LDH-A활성증고인기NIT-1세포이도소분비결함；ROS격활LDH-A가능시이도β세포포도당독성적궤제지일。
Objective:To investigate the relationship between lactate dehydrogenase-A (LDH-A) activity and insulin secretion under chronic high-glu-cose 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 ex-amined. 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 oc-curred 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.