Multifaceted Interweaving Between Extracellular Matrix, Insulin Resistance, and Skeletal Muscle

Abstract

The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides integrity and biochemical signals and plays an important role in myogenesis. In addition, it undergoes remodeling upon injury and/or repair, which is also related to insulin resistance (IR), a major cause of type 2 diabetes (T2DM). Altered signaling of integrin and ECM remodeling in diet-induced obesity is associated with IR. This review highlights the interweaving relationship between the ECM, IR, and skeletal muscle. In addition, the importance of the ECM in muscle integrity as well as cellular functions is explored. IR and skeletal muscle ECM remodeling has been discussed in clinical and nonclinical aspects. Furthermore, this review considers the role of ECM glycation and its effects on skeletal muscle homeostasis, concentrating on advanced glycation end products (AGEs) as an important risk factor for the development of IR. Understanding this complex interplay between the ECM, muscle, and IR may improve knowledge and help develop new ideas for novel therapeutics for several IR-associated myopathies and diabetes.

Cross-Talk Between Extracellular Matrix and Skeletal Muscle: Implications for Myopathies

“…Several SM-associated genetic disorders are typically caused by mutations in ECM elements and cell surface receptors. Interestingly, more than 150 ECM proteins have been reported to interact with integrin receptors (Zaidel-Bar et al, 2007;Ahmad et al, 2018).…”

“…SM supports skeletal development, aids skeletal movement, controls body temperature, and manages glucose uptake and is composed of large numbers of long, multinucleated filaments, which are organized by extracellular matrix (ECM) (Davis et al, 2013). ECM plays important roles during wound healing, embryogenesis, and tissue repair and provides integrity and biochemical signals to cells (Govindan and Iovine, 2015;Ahmad et al, 2018) and is composed of glycoproteins like collagens, fibronectin (FN), and laminins (Frantz et al, 2010) (Figure 1). Furthermore, two major SM ECM proteins, that is, collagen and laminin, are known to be associated with myopathies.…”

Role of elastin peptides and elastin receptor complex in metabolic and cardiovascular diseases

“…Thus, free fatty acids and glucose, proinflammatory cytokines as TNF (Tumor Necrosis Factor)-a or IL (interleukin)-1b, secreted for example by adipose tissue, are involved in insulin resistance. Interestingly, the glucose intolerance and hyperinsulinism, gradually developing, induce an important remodeling of extracellular matrix [36]. During adipocytes hypertrophy, the matrix is degraded by proteases to allow the increase in lipid droplet volume [37][38][39].…”

Transthyretin Maintains Muscle Homeostasis through the Novel Shuttle Pathway of Thyroid Hormones during Myoblast Differentiation

“…Skeletal muscle is comprised of multinucleated myofibers and has excellent regeneration capability, which deteriorates progressively with age, restraining the voluntary functions of daily life. The regenerative capacity is mostly facilitated by muscle satellite or stem cells (MSCs) that reside between the basal lamina and sarcolemma, a distinct 'niche' in the muscle fibers [1,2]. MSCs vigorously regulate myofiber growth, and MSC progression is typically regulated by the expression of myogenic transcription factors (Pax3, Pax7, myoblast determination protein; MYOD, and myogenin; MYOG) [3].…”