Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2015; 6(2): 217-224
Published online Mar 15, 2015. doi: 10.4239/wjd.v6.i2.217
mTOR: Driving apoptosis and autophagy for neurocardiac complications of diabetes mellitus
Kenneth Maiese
Kenneth Maiese, Cellular and Molecular Signaling, Newark, NJ 07101, United States
Author contributions: Maiese K conceived, designed, and wrote this article.
Supported by The following grants to Kenneth Maiese: American Diabetes Association; American Heart Association; NIH NIEHS; NIH NIA; NIH NINDS; and NIH ARRA.
Conflict-of-interest: The author declares no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Kenneth Maiese, MD, Cellular and Molecular Signaling, Newark, NJ 07101, United States. wntin75@yahoo.com
Received: November 2, 2014
Peer-review started: November 2, 2014
First decision: November 27, 2014
Revised: December 10, 2014
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: March 15, 2015
Abstract

The World Health Organization estimates that diabetes mellitus (DM) will become the seventh leading cause of death during the next two decades. DM affects approximately 350 million individuals worldwide and additional millions that remain undiagnosed are estimated to suffer from the complications of DM. Although the complications of DM can be seen throughout the body, the nervous, cardiac, and vascular systems can be significantly affected and lead to disorders that include cognitive loss, stroke, atherosclerosis, cardiac failure, and endothelial stem cell impairment. At the cellular level, oxidative stress is a significant determinant of cell fate during DM and leads to endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis, and autophagy. Multiple strategies are being developed to combat the complications of DM, but it is the mechanistic target of rapamycin (mTOR) that is gaining interest in drug development circles especially for protective therapies that involve cytokines and growth factors such as erythropoietin. The pathways of mTOR linked to mTOR complex 1, mTOR complex 2, AMP activated protein kinase, and the hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) complex can ultimately influence neuronal, cardiac, and vascular cell survival during oxidant stress in DM through a fine interplay between apoptosis and autophagy. Further understanding of these mTOR regulated pathways should foster novel strategies for the complications of DM that impact millions of individuals with death and disability.

Keywords: Apoptosis, Autophagy, Cardiac disease, Diabetes mellitus, Erythropoietin, Metformin, Oxidative stress, Neurodegeneration, Mechanistic target of rapamycin, Vascular disease

Core tip: The pathways of mechanistic target of rapamycin (mTOR) linked to mTOR complex 1, mTOR complex 2, AMP activated protein kinase, and tuberous sclerosis 1/tuberous sclerosis 2 complex can offer novel strategies for the complications of diabetes mellitus to prevent death and disability for the millions of individuals afflicted with this disorder.