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

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Shi, Ting-Ting
Yang, Fang-Yuan
Liu, Chang
Cao, Xi
Lu, Jing
Zhang, Xue-Lian
Yuan, Ming-Xia
Chen, Chen
Yang, Jin-Kui
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2018
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Abstract

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 2 O 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 −/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.

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Biochemical and Biophysical Research Communications

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495

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1

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Medicinal and biomolecular chemistry

Biochemistry and cell biology

Medical biochemistry and metabolomics

Science & Technology

Life Sciences & Biomedicine

Biochemistry & Molecular Biology

Biophysics

ACE2

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Shi, T-T; Yang, F-Y; Liu, C; Cao, X; Lu, J; Zhang, X-L; Yuan, M-X; Chen, C; Yang, J-K, Angiotensin-converting enzyme 2 regulates mitochondrial function in pancreatic beta-cells, Biochemical and Biophysical Research Communications, 2018, 495 (1), pp. 860-866

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