1. Academic Validation
  2. Autoantibody against angiotensin II type I receptor induces pancreatic β-cell apoptosis via enhancing autophagy

Autoantibody against angiotensin II type I receptor induces pancreatic β-cell apoptosis via enhancing autophagy

  • Acta Biochim Biophys Sin (Shanghai). 2021 May 21;53(6):784-795. doi: 10.1093/abbs/gmab049.
Jin Wang 1 Dan Li 1 Zhinan Zhang 1 Yan Zhang 1 Zhandong Lei 1 Wenwen Jin 1 Jimin Cao 1 Xiangying Jiao 1
Affiliations

Affiliation

  • 1 Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Abstract

Autoantibody against the angiotensin II type I receptor (AT1-AA) has been found in the serum of patients with diabetes mellitus (DM). However, it remains unclear whether AT1-AA induces β-cell Apoptosis and participates in the development of DM. In this study, an AT1-AA-positive rat model was set up by active immunization, and AT1-AA IgG was purified. INS-1 cells were treated with AT1-AA, and cell viability, Apoptosis, and autophagy-related proteins were detected by Cell Counting Kit-8 assay, flow cytometry, and western blot analysis, respectively. Results showed that existence of AT1-AA impaired the islet function and increased the Apoptosis of pancreatic islet cells in rats, and the Autophagy level in rat pancreatic islet tissues tended to increase gradually with the prolongation of immunization time. AT1-AA markedly reduced INS-1 cell viability, promoted cell Apoptosis, and decreased Insulin secretion in vitro. In addition, the Autophagy level was gradually increased along with the prolongation of AT1-AA treatment time. Meanwhile, it was determined that treatment with Autophagy Inhibitor 3-methyladenine and angiotensin II type 1 receptor (AT1R) blocker telmisartan could improve Insulin secretion and Apoptosis in vitro and in vivo. In conclusion, it is deduced that upregulation of Autophagy contributed to the AT1-AA-induced β-cell Apoptosis and islet dysfunction, and AT1R mediated the signal transduction.

Keywords

angiotensin II type I receptor; apoptosis; autoantibody; autophagy; β cell.

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