Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

Abstract

There are numerous lines of clinical evidence that inhibition of the renin–angiotensin system (RAS) can prevent and delay the development of diabetes. Also, the role of RAS in the pathogenesis of diabetes, including insulin resistance and β‐cell dysfunction, has been extensively investigated. Nevertheless, this role had not yet been fully shown. A variety of possible protective mechanisms for RAS blockers in the regulation of glucose homeostasis have been suggested. However, the direct effect on pancreatic islet fibrosis has only recently been spotlighted. Various degrees of islet fibrosis are often observed in the islets of patients with type 2 diabetes mellitus, which can be associated with a decrease in β‐cell mass and function in these patients. Pancreatic stellate cells are thought to be deeply involved in this islet fibrosis. In this process, the activation of RAS in islets is shown to transform quiescent pancreatic stellate cells into the activated form, stimulates their proliferation and consequently leads to islet fibrotic destruction. In this article, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of RAS, and review the responsible local RAS signaling pathways in pancreatic stellate cells. Finally, we propose possible targets for the prevention of islet fibrosis.

Abstract

In this review, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of the renin–angiotensin system, and review the responsible local renin–angiotensin system signaling pathways in pancreatic stellate cells involved in islet fibrosis. Finally, we propose possible targets for the prevention of islet fibrosis.