Abstract

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.

Highlights

  • Abundant nutrient intake in combination with decreased exercise contributes to the global epidemic of obesity and type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance and/or pancreatic beta cell dysfunction [1]

  • According to the expression profiling data, 264 significantly dysregulated Long noncoding RNAs (lncRNAs) were identified with a set filter in the high glucose and palmitate (HG/PA)-treated INS-1 cells: 153 were upregulated, while 111 were downregulated

  • We identified the changes of lncRNA expression in INS-1 cells treated by HG/PA for the first time

Read more

Summary

Introduction

Abundant nutrient intake in combination with decreased exercise contributes to the global epidemic of obesity and type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance and/or pancreatic beta cell dysfunction [1]. A common feature of T2DM individuals is elevated blood glucose and/or high serum free fatty acids (FFA) [2]. Oxidative Medicine and Cellular Longevity of hyperglycemia causes beta cell failure characterized by impaired insulin secretion and enhanced islet beta cell apoptosis (glucotoxicity) [3, 4]. Long-term exposure of beta cells to FFA triggers apoptosis (lipotoxicity) and the elevated glucose augments fatty acid-induced beta cell death (glucolipotoxicity) [5,6,7]. The molecular mechanisms involved in glucolipotoxicity-induced beta cell dysfunction are not fully understood

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call