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World J Diabetes. Jul 15, 2021; 12(7): 1081-1092
Published online Jul 15, 2021. doi: 10.4239/wjd.v12.i7.1081
Role and function of granin proteins in diabetes mellitus
Zoltan Herold, Marton Doleschall, Aniko Somogyi
Zoltan Herold, Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest 1083, Hungary
Zoltan Herold, Aniko Somogyi, Department of Internal Medicine and Hematology, Semmelweis University, Budapest 1088, Hungary
Marton Doleschall, Molecular Medicine Research Group, Eotvos Lorand Research Network and Semmelweis University, Budapest 1089, Hungary
Author contributions: Herold Z and Doleschall M searched the literature and drafted initial manuscript; Somogyi A provided further editing and comments; all authors have read and agreed to the published version of the manuscript.
Supported by the UNKP-20-4-I New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zoltan Herold, MSc, Research Scientist, Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Tomo u. 25-29, Budapest 1083, Hungary. herold.zoltan@med.semmelweis-univ.hu
Received: January 27, 2021
Peer-review started: January 27, 2021
First decision: February 25, 2021
Revised: March 5, 2021
Accepted: May 17, 2021
Article in press: May 17, 2021
Published online: July 15, 2021
Processing time: 165 Days and 18.4 Hours
Abstract

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, CgA10-19, and CgA43-52 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.

Keywords: Granin; Chromogranin A; Chromogranin B; Diabetes Mellitus; Mice; Inbred nonobese diabetic; Secretogranin III

Core Tip: Granin glycoproteins are secretory proteins that are widely produced by neuronal, neuroendocrine, and endocrine cells throughout the human body. Recent data have shown that the granin proteins chromogranin A and B, and secretogranin II and III play a role in carbohydrate metabolism and in the pathophysiology of diabetes mellitus. In this review, the current state of knowledge concerning the relationship between granin proteins, diabetes and glucose homeostasis is discussed in detail, including several ongoing studies investigating granin-based drug therapies of future promise in diabetes care.