Role and function of granin proteins in diabetes mellitus

The granin glycoprotein family consists of nine acidic proteins; chromogranin A (CgA), chromogranin B (CgB), and secretogranin II-VIII. They are produced by a wide range of neuronal, neuroendocrine, and endocrine cells throughout the human body. Their major intracellular function is to sort peptides and proteins into secretory granules, but their cleavage products also take part in the extracellular regulation of diverse biological processes. The contribution of granins to carbohydrate metabolism and diabetes mellitus is a recent research area. CgA is associated with glucose homeostasis and the progression of type 1 diabetes. WE-14, CgA_10-19, and CgA_43-52 are peptide derivates of CgA, and act as CD4⁺ or CD8⁺ autoantigens in type 1 diabetes, whereas pancreastatin (PST) and catestatin have regulatory effects in carbohydrate metabolism. Furthermore, PST is related to gestational and type 2 diabetes. CgB has a crucial role in physiological insulin secretion. Secretogranins II and III have angiogenic activity in diabetic retinopathy (DR), and are novel targets in recent DR studies. Ongoing studies are beginning to investigate the potential use of granin derivatives as drugs to treat diabetes based on the divergent relationships between granins and different types of diabetes.