Effect of RAS on islets β-cell function and the role and the mechanism in which AT1R involves / 中华内分泌代谢杂志

ABSTRACT

Objective To study the role of pancreatic renin-angiotensin system (RAS) on insulin secretion, proliferation, apoptosis, oxidative stress, and fibrosis of β-cells. Methods The effect of angiotensin Ⅱ on βTC3 cells was studied and the role and mechanism of AT1 R were analyzed with RNAi technology. The expression of AT1 R was measured by Western Blotting. The change of intracellular calcium was detected by microfluorimetry with Furo3-1oaded cells. Peroxide-sensitive fluorescent probe DCFH-DA was used to analyze intracellular ROS by flow cytometry. Real-time PCR was performed to evaluate mRNA levels related to proliferation and fibrosis in βTC3 cells. Apoptosis was detected by flow cytometry and Tunel method. Results Insulin secretion was significantly increased up to four fold and the level of intracellular calcium was sharply increased in response to high glucose in βTC3 cells. Angiotensin Ⅱ has no direct effect on insulin secretion in βTC3 cells and its role in secretion was associated with the role in proliferation. Oxidative stress in βTC3 cells caused by angiotensin Ⅱ may be partially mediated through AT1R, protein kinase C and NAD(P) H. With the decrease of AT1R expression by RNAi technology, apoptosis, and fibrosis of βTC3 cells induced by angiotensin Ⅱ might be ameliorated.Conclusions By means of AT1R, angiotensin Ⅱ plays an important role in insulin secretion, proliferation,apoptosis, oxidative stress and fibrosis in β-cells.