Angiotensin-converting enzyme 2 regulates mitochondrial function in pancreatic β-cells

Biochem Biophys Res Commun. 2018 Jan 1;495(1):860-866. doi: 10.1016/j.bbrc.2017.11.055. Epub 2017 Nov 9.


Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells. PCR array demonstrated that ACE2 over-expression up-regulated 67 mitochondria-related genes in INS-1 cells. In pancreatic islets, ACE2 ablation attenuated intracellular calcium influx with a decrease in GSIS. Ace2-/y mice islets exhibited impaired mitochondrial respiration and lower production of ATP, along with decreased expression of genes involved in mitochondrial oxidation. In islets from db/db mice, ACE2 over-expression increased intracellular calcium influx and restored impaired mitochondrial oxidation, potentially causing an increase in GSIS. These results shed light on the potential roles of ACE2 in mitochondrial metabolism, moreover, may improve our understanding of diabetes.

Keywords: ACE2; Insulin secretion; Intracellular calcium; Mitochondrial metabolism; Pancreatic β-cells.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Calcium Signaling / physiology
  • Gene Expression Regulation, Enzymologic / physiology
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Oxygen Consumption / physiology
  • Peptidyl-Dipeptidase A / metabolism*


  • Insulin
  • Mitochondrial Proteins
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Glucose