The Effects of Renin‐Angiotensin System on Endoplasmic Reticulum Stress in Pancreatic Beta Cells

Abstract

Type 2 diabetes is an emerging epidemic and affects more than 25 million people in the United States. The Renin Angiotensin System (RAS) is classically known to regulate blood pressure and fluid balance. Interestingly, components of RAS, including the product angiotensin II (Ang II), which is the active hormone of this system, are expressed in both adipose tissues and pancreas. Studies conducted in our laboratory have shown that mice overexpressing RAS specifically in adipose tissue had insulin resistance, higher levels of inflammation, and endoplasmic reticulum (ER) stress. However, no studies have investigated the relationship between RAS and ER stress in beta cells. Hence, we hypothesized that activation of RAS in beta cells leads to increased ER stress and reduced insulin secretion. To test this hypothesis, we treated clonal beta cells with Ang II, and found that Ang II significantly increased the expression of ER stress genes such as CHOP and ATF4. In addition, Ang II treatments also reduced insulin secretion. Furthermore, inhibition of Ang II production in beta cells using an angiotensin converting enzyme inhibitor (ACEi) significantly reduced ER stress. Additionally, pharmacological inhibition of angiotensin type I and II receptors significantly reduced ER stress. These results indicate involvement of the RAS pathway in ER stress in pancreatic beta cells. We are currently determining effects of these RAS inhibitors on insulin secretion. In conclusion, this research will help better understand the role of RAS activation via ER stress on diabetes progression and may help develop new anti‐diabetes therapeutic targets.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.