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Review
. 2020 May 28;21(11):3845.
doi: 10.3390/ijms21113845.

Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective

Khurshid Ahmad  1 , Inho Choi  1 , Yong-Ho Lee  2
Affiliations
Review

Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective

Khurshid Ahmad et al. Int J Mol Sci. .

Abstract

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.

Keywords: diabetes; extracellular matrix; insulin resistance; integrin; remodeling.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Glucose uptake mechanism via insulin-mediated translocation of GLUT4. (A) Insulin binds to the insulin receptor, activating autophosphorylation and PI3K, which activates AKT followed by translocation of vesicles containing GLUT4 from the intracellular compartment to the surface membrane. GLUT4 inserts into the membrane and triggers the uptake of glucose. (B) Disturbance in the activation of PI3K and AKT pathways disrupts the GLUT4 translocation that eventually results in the development of insulin resistance (IR) [arrow shows the next step of the process and cross shows the disruption of the process].
Figure 2
Figure 2
Illustration of interacting pathways and genes with SLC2A4 (GLUT4).
Figure 3
Figure 3
Schematic representation of extracellular matrix (ECM) remodeling in skeletal muscle.
See this image and copyright information in PMC

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