Angiotensin(1–7) Improves Islet Function in Diabetes Through Reducing JNK/Caspase-3 Signaling

Abstract

The aim of this study is to investigate whether Angiotensin (1–7), the physiological antagonist of Angiotensin II (AngII), has antidiabetic activity and the possible mechanism. Male Wistar rats were randomly divided into 3 groups: control group fed the normal diet, DM group fed high-fat diet and injected with STZ, and Angiotensin (1–7) group receiving injection of STZ followed by Angiotensin (1–7) treatment. Serum Ang II, fasting blood glucose, insulin, HOMA-IR, and HOMA-beta were determined in control, diabetes and Angiotensin (1–7) groups. The increased AngII and insulin resistance in diabetes group were accompanied by changes in islet histopathology. However, Angiotensin (1–7) improved the islet function and histopathology in diabetes without affecting the level of AngII. Western blot confirmed that Angiotensin (1–7) decreased the cleaved caspase 3 levels in pancreas of DM. The increased expression of JNK, Bax, and Bcl2 genes under diabetic conditions were partially reversed after Angiotensin (1–7) administration in pancreas. Immunofluorescence analysis showed that p-JNK was markedly increased in islet of DM rats, which was markedly alleviated after Angiotensin (1–7) treatment. Furthermore, Angiotensin (1–7) reversed high glucose(HG) induced mitochondrial apoptosis augments. Finally, Angiotensin (1–7) attenuated the apoptosis of INS-1 cells through reducing JNK activation in diabetes, which was blocked by anisomycin (a potent agonist of JNK). Our findings provide supporting evidence that Angiotensin (1–7) improved the islet beta-cells apoptosis by JNK-mediated mitochondrial dysfunction, which might be a novel target for the treatment and prevention of beta-cells dysfunction in DM.

Key words

angiotensin(1–7) - apoptosis - beta cells - diabetes mellitus type 2

Publication History

Received: 25 September 2021

Accepted after revision: 23 February 2022

Article published online:
12 April 2022

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