The angiotensin-converting enzyme 2/angiotensin (1-7)/Mas axis protects the function of pancreatic β cells by improving the function of islet microvascular endothelial cells

Lu,Chun-Li; Wang,Ying; Yuan,Li; Li,Yang; Li,Xiao-Ya

doi:10.3892/ijmm.2014.1917

The angiotensin-converting enzyme 2/angiotensin (1-7)/Mas axis protects the function of pancreatic β cells by improving the function of islet microvascular endothelial cells

Authors:
- Chun-Li Lu
- Ying Wang
- Li Yuan
- Yang Li
- Xiao-Ya Li
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Affiliations: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: August 28, 2014 https://doi.org/10.3892/ijmm.2014.1917
Pages: 1293-1300

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Abstract

In the diabetic state, the local rennin-angiotensin system (RAS) is activated in the pancreas, and is strongly associated with islet dysfunction. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis is a protective, negative regulator of the classical renin-angiotensin system. In this study, we assessed the role of the ACE2/Ang(1‑7)/Mas axis in pancreatic β cell survival and function. ACE2 knockout and wild-type mice were fed a high-fat diet for 16 weeks. We then performed terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and determined the expression levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in the pancreatic islets. The effects of Ang(1-7) or Mas receptor silencing on endothelial function were assessed in MS-1 cells. MIN6 cells were then co-cultured with the MS-1 cells to evaluate the effects of ACE2 on insulin secretion. The ACE2 knockout mice were more susceptible than the wild-type mice to high-fat diet-induced β cell dysfunction. The TUNEL-positive area of the pancreatic islets and the expression levels of IL-1β and iNOS were markedly increased in the ACE2 knockout mice compared with their wild-type littermates. The Mas-silenced MS-1 cells were more sensitive to palmitate-induced dysfunction and apoptosis in vitro. Ang(1-7) increased the activity of the Akt/endothelial NOS/nitric oxide (NO) pathway in the MS-1 cells, protected MIN6 cells against palmitate-induced apoptosis, and improved MIN6 insulin secretory function in the co-culture system. In conclusion, this study demonstrates that the ACE2/Ang(1-7)/Mas axis is a potential target for protecting the funcion of β cells by improving the function of islet microvascular endothelial cells.

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