Isletopathy in Type 2 Diabetes Mellitus: Implications of Islet RAS, Islet Fibrosis, Islet Amyloid, Remodeling, and Oxidative Stress

This review focuses primarily on islet structural and functional changes related to an activated islet renin- angiotensin system (RAS), islet oxidative-redox imbalance, the concurrence of islet fibrosis (pericapillary, intra- and peri-islet), and islet amyloid deposition (pericapillary, intra- and peri-islet). The islet-acinar-portal vascular pathway and the emerging important anatomical and functional region, the islet-exocrine interface, are also discussed. Because there is an associated histopathological islet disease in type 2 diabetes mellitus (T2DM), the term isletopathy is discussed in detail. The isletopathy in T2DM is equally important as the other complications of diabetes. Special stains and special lighting (bright field and crossed polarized light) are utilized, along with light and transmission electron microscopy, in order to better understand islet structural remodeling in T2DM. The importance of an isletopathy in T2DM is supported by numerous remodeling changes within the islet and the islet-exocrine interface. While some of the structural findings are only preliminary observations, additional investigation in this area should lead to the development of new pathophysiological concepts and new therapies regarding the prevention and treatment of T2DM.