Increased COX6A2 Promotes Pancreatic β-Cell Apoptosis and Is Suppressed in Diabetic GK Rats After Roux-en-Y Gastric Bypass

Diabetes. 2025 Feb 1;74(2):175-187. doi: 10.2337/db24-0301.

Abstract

Cytochrome c oxidase subunit 6A2 (COX6A2) expression is increased in diabetic islets. Increased COX6A2 promotes β-cell apoptosis via modulation of cyclophilin D-mediated cytochrome c release from mitochondria to the cytoplasm. Carbohydrate-responsive element-binding protein epigenetically regulates COX6A2 expression in β-cells. Roux-en-Y gastric bypass reduces COX6A2 expression by regulating the glucagon-like peptide 1/cAMP-dependent protein kinase/carbohydrate-responsive element-binding protein signaling pathway.

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Gastric Bypass*
  • Glucagon-Like Peptide 1 / metabolism
  • Insulin-Secreting Cells* / metabolism
  • Insulin-Secreting Cells* / pathology
  • Male
  • Rats
  • Signal Transduction / physiology

Substances

  • Electron Transport Complex IV
  • Glucagon-Like Peptide 1