pancreastatin and Diabetes-Mellitus--Type-1

Chromogranin A is a member of the granin glycoprotein family that is expressed by the endocrine and neuroendocrine cells of different organs. Intracellularly, chromogranin A contributes to the regulation of secretion and gives several cleavage products after secretion. Some of its cleavage products modify the hormone functions in autocrine and paracrine ways, while the functions of others have not been fully understood yet. Serum chromogranin A level is most prominently used in neuroendocrine tumour diagnostics. In addition, recent studies have suggested that chromogranin A and some of its cleavage products (pancreastatin and WE-14) also play important roles in the pathogenesis of the various forms of diabetes mellitus, but their exact mechanisms still need to be clarified. Higher chromogranin A, pancreastatin, and WE-14 levels have been reported in type 1, type 2, and gestational diabetic patients compared to healthy controls. A notable connection has been inferred through the observation that type 1 diabetes mellitus is not at all or rarely developed in chromogranin A gene-knockout, non-obese diabetic model mice compared to non-knockout, non-obese diabetic mice. Pancreastatin inhibits insulin release in various cell and animal models, and WE-14 serves as an autoantigen for both CD4+ and CD8+ beta cell-destructive diabetogenic T-cell clones in type 1 diabetes. Chromogranin A contributes to the pathogenesis of diabetes mellitus according to the available literature. The current findings facilitate further investigation to unravel the deeper relationships between this glycoprotein and diabetes.

Topics: Animals; Chromogranin A; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Mice; Mice, Inbred NOD; Pregnancy

Chromogranin A (CgA) is an established plasma marker of neuroendocrine tumors and has been suggested to also have a role as biomarker in other diseases. Whether CgA has any role as biomarker in diabetes is, however, unresolved, but its widespread distribution in the secretory granules in endocrine tissues including β cells and α cells in pancreas, and the metabolic effects of its peptide fragments suggest that CgA may play a pathophysiological role in diabetes, and thus also be a potential diabetes biomarker. In this review, we summarize the available information on CgA and some of its functional post-translational cleavage products in diabetes, followed by a discussion of its potential as a plasma marker in diabetes and the methodological concerns involved.

Topics: Biomarkers; Chromogranin A; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin-Secreting Cells