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World J Diabetes. Mar 15, 2022; 13(3): 213-223
Published online Mar 15, 2022. doi: 10.4239/wjd.v13.i3.213
Humanin and diabetes mellitus: A review of in vitro and in vivo studies
Chrysoula Boutari, Panagiotis D Pappas, Theodoros D Theodoridis, Dimitrios Vavilis
Chrysoula Boutari, Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
Panagiotis D Pappas, Theodoros D Theodoridis, Dimitrios Vavilis, First Department of Obstetrics and Gynaecology, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
Dimitrios Vavilis, Medical School, University of Cyprus, Nicosia, Cyprus 20537 1678, Cyprus
Author contributions: All authors contributed equally to the writing of the manuscript and have read and approve the final manuscript.
Conflict-of-interest statement: There are 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: Chrysoula Boutari, MD, MSc, PhD, Associate Specialist, Doctor, Instructor, Postdoc, Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University of Thessaloniki, 49, Konstantinoupoleos Street, Thessaloniki 54642, Greece. chrisoulabgr@yahoo.gr
Received: August 30, 2021
Peer-review started: August 30, 2021
First decision: October 3, 2021
Revised: October 24, 2021
Accepted: February 23, 2022
Article in press: February 23, 2022
Published online: March 15, 2022
Abstract

Humanin (HN) is a 24-amino acid mitochondrial-derived polypeptide with cyto-protective and anti-apoptotic effects that regulates the mitochondrial functions under stress conditions. Accumulating evidence suggests the role of HN against age-related diseases, such as Alzheimer’s disease. The decline in insulin action is a metabolic feature of aging and thus, type 2 diabetes mellitus is considered an age-related disease, as well. It has been suggested that HN increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes, actions that could be deployed in the treatment of diabetes. The aim of this review is to present the in vitro and in vivo studies that examined the role of HN in insulin resistance and diabetes and to discuss its newly emerging role as a therapeutic option against those conditions.

Keywords: Diabetes mellitus, Insulin resistance, Humanin, Aging, Apoptosis, Oxidative stress

Core Tip: Humanin (HN) exerts cyto-protective and anti-apoptotic effects. Type 2 diabetes mellitus (T2DM) is considered an age-related disease. Beyond the role of HN against age-related diseases, it increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes. Altered HN levels could serve as a potential biomarker in prediabetes and T2DM, since they seem to be an effect or a response to the increased reactive oxygen species production, oxidative stress, and reduced mitochondrial DNA copy number-A major and important question is whether HN could be used as a potential therapeutic option for diabetes.