Cordycepin protects islet β-cells against glucotoxicity and lipotoxicity via modulating related proteins of ROS/JNK signaling pathway

Biomed Pharmacother. 2023 Jul:163:114776. doi: 10.1016/j.biopha.2023.114776. Epub 2023 Apr 24.

Abstract

Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.

Keywords: Apoptosis; Cordycepin; Diabetes; Glucotoxicity; INS-1 cell; Lipotoxicity.

MeSH terms

  • Animals
  • Apoptosis
  • Diabetes Mellitus, Type 2* / metabolism
  • Glucose / metabolism
  • Insulin / metabolism
  • Insulin-Secreting Cells*
  • Lipids / pharmacology
  • MAP Kinase Signaling System
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • cordycepin
  • Glucose
  • Insulin
  • Lipids
  • Reactive Oxygen Species
  • RNA, Messenger