O'Reilly CL, Uranga S, Fluckey JD. Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes. World J Biol Chem 2021; 12(5): 70-86 [PMID: 34630911 DOI: 10.4331/wjbc.v12.i5.70]
Corresponding Author of This Article
James D Fluckey, PhD, Professor, Health and Kinesiology, Texas A&M University, TAMU 4243, College Station, TX 77843, United States. jfluckey@tamu.edu
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Review
Open-Access Policy of This Article
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/
World J Biol Chem. Sep 27, 2021; 12(5): 70-86 Published online Sep 27, 2021. doi: 10.4331/wjbc.v12.i5.70
Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes
Colleen L O'Reilly, Selina Uranga, James D Fluckey
Colleen L O'Reilly, Selina Uranga, James D Fluckey, Health and Kinesiology, Texas A&M University, TX 77843, United States
Author contributions: O’Reilly CL wrote the majority of the review; Uranga S contributed to the writing, designed and produced the figures; Fluckey JD contributed to the writing and edited the manuscript.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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: James D Fluckey, PhD, Professor, Health and Kinesiology, Texas A&M University, TAMU 4243, College Station, TX 77843, United States. jfluckey@tamu.edu
Received: March 31, 2021 Peer-review started: March 31, 2021 First decision: June 7, 2021 Revised: June 21, 2021 Accepted: August 3, 2021 Article in press: August 3, 2021 Published online: September 27, 2021
Abstract
The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Skeletal muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2D research. Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits vs consequences of the disease has been elusive. Emerging evidence in skeletal muscle implicates influential cross talk between a key anabolic regulatory protein, the mammalian target of rapamycin (mTOR) and its associated complexes (mTORC1 and mTORC2), and the well-described canonical signaling for insulin-stimulated glucose uptake. This new understanding of cellular signaling crosstalk has blurred the lines of what is a culprit and what is a consequence with regard to insulin resistance. Here, we briefly review the most recent understanding of insulin signaling in skeletal muscle, and how anabolic responses favoring anabolism directly impact cellular glucose disposal. This review highlights key cross-over interactions between protein and glucose regulatory pathways and the implications this may have for the design of new therapeutic targets for the control of glucoregulatory function in skeletal muscle.
Core Tip: The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits vs consequences of the disease has been elusive. Emerging evidence in skeletal muscle implicates influential cross talk between the mammalian target of rapamycin (mTOR) complexes (mTORC1 and mTORC2) during insulin stimulated glucose uptake. This review highlights interactions between protein and glucose regulatory pathways and the implications this may have for the control of glucoregulatory function in skeletal muscle.
