Angiotensin-converting enzyme 2 regulates mitochondrial function in pancreatic β-cells
- Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 (China)
- Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730 (China)
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD, 4072 (Australia)
Highlights: • ACE2 improved glucose stimulated insulin secretion (GSIS) and mitochondrial membrane potential in INS-1 cells. • PCR array demonstrated that ACE2 up-regulated 67 mitochondria-related genes in INS-1 cells. • ACE2 deletion suppressed mitochondrial oxidation and calcium influx in islets. • ACE2 over-expression in db/db mice promoted mitochondrial oxidation and calcium influx in islets. 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 H{sub 2}O{sub 2} 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{sup −/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.
- OSTI ID:
- 23134492
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 495, Issue 1; Other Information: Copyright (c) 2017 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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