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17 pages, 12032 KiB

Open AccessArticle

Investigating the Causal Effects of Exercise-Induced Genes on Sarcopenia

by Li Wang and Song Zhang

Int. J. Mol. Sci. 2024, 25(19), 10773; https://doi.org/10.3390/ijms251910773 - 7 Oct 2024

Viewed by 1210

Abstract

Exercise is increasingly recognized as an effective strategy to counteract skeletal muscle aging and conditions such as sarcopenia. However, the specific exercise-induced genes responsible for these protective effects remain unclear. To address this, we conducted an eight-week aerobic exercise regimen on late-middle-aged mice [...] Read more.

Exercise is increasingly recognized as an effective strategy to counteract skeletal muscle aging and conditions such as sarcopenia. However, the specific exercise-induced genes responsible for these protective effects remain unclear. To address this, we conducted an eight-week aerobic exercise regimen on late-middle-aged mice and developed an integrated approach that combines mouse exercise-induced genes with human GWAS datasets to identify causal genes for sarcopenia. This approach led to significant improvements in the skeletal muscle phenotype of the mice and the identification of exercise-induced genes and miRNAs. By constructing a miRNA regulatory network enriched with transcription factors and GWAS signals related to muscle function and traits, we focused on 896 exercise-induced genes. Using human skeletal muscle cis-eQTLs as instrumental variables, 250 of these exercise-induced genes underwent two-sample Mendelian randomization analysis, identifying 40, 68, and 62 causal genes associated with sarcopenia and its clinical indicators—appendicular lean mass (ALM) and hand grip strength (HGS), respectively. Sensitivity analyses and cross-phenotype validation confirmed the robustness of our findings. Consistently across the three outcomes, RXRA, MDM1, RBL2, KCNJ2, and ADHFE1 were identified as risk factors, while NMB, TECPR2, MGAT3, ECHDC2, and GINM1 were identified as protective factors, all with potential as biomarkers for sarcopenia progression. Biological activity and disease association analyses suggested that exercise exerts its anti-sarcopenia effects primarily through the regulation of fatty acid oxidation. Based on available drug–gene interaction data, 21 of the causal genes are druggable, offering potential therapeutic targets. Our findings highlight key genes and molecular pathways potentially responsible for the anti-sarcopenia benefits of exercise, offering insights into future therapeutic strategies that could mimic the safe and mild protective effects of exercise on age-related skeletal muscle degeneration. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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14 pages, 5805 KiB

Open AccessArticle

Skeletal Muscle UCHL1 Negatively Regulates Muscle Development and Recovery after Muscle Injury

by Ryan Antony, Katherine Aby, Morgan Montgomery and Yifan Li

Int. J. Mol. Sci. 2024, 25(13), 7330; https://doi.org/10.3390/ijms25137330 - 4 Jul 2024

Viewed by 1135

Abstract

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme originally found in the brain. Our previous work revealed that UCHL1 was also expressed in skeletal muscle and affected myoblast differentiation and metabolism. In this study, we further tested the role of UCHL1 in [...] Read more.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme originally found in the brain. Our previous work revealed that UCHL1 was also expressed in skeletal muscle and affected myoblast differentiation and metabolism. In this study, we further tested the role of UCHL1 in myogenesis and muscle regeneration following muscle ischemia-reperfusion (IR) injury. In the C2C12 myoblast, UCHL1 knockdown upregulated MyoD and myogenin and promoted myotube formation. The skeletal muscle-specific knockout (smKO) of UCHL1 increased muscle fiber sizes in young mice (1 to 2 months old) but not in adult mice (3 months old). In IR-injured hindlimb muscle, UCHL1 was upregulated. UCHL1 smKO ameliorated tissue damage and injury-induced inflammation. UCHL1 smKO also upregulated myogenic factors and promoted functional recovery in IR injury muscle. Moreover, UCHL1 smKO increased Akt and Pink1/Parkin activities. The overall results suggest that skeletal muscle UCHL1 is a negative factor in skeletal muscle development and recovery following IR injury and therefore is a potential therapeutic target to improve muscle regeneration and functional recovery following injuries. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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15 pages, 1990 KiB

Open AccessArticle

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats

by Mandlakazi Dlamini and Andile Khathi

Int. J. Mol. Sci. 2024, 25(7), 4076; https://doi.org/10.3390/ijms25074076 - 6 Apr 2024

Cited by 1 | Viewed by 1509

Abstract

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the [...] Read more.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6–6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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16 pages, 2911 KiB

Open AccessArticle

Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome

by Daniel Alexander Bizjak, Birgit Ohmayer, Jasmine Leonike Buhl, Elisabeth Marion Schneider, Paul Walther, Enrico Calzia, Achim Jerg, Lynn Matits and Jürgen Michael Steinacker

Int. J. Mol. Sci. 2024, 25(3), 1675; https://doi.org/10.3390/ijms25031675 - 30 Jan 2024

Cited by 7 | Viewed by 6539

Abstract

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology [...] Read more.

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs). Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC. While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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16 pages, 2503 KiB

Open AccessArticle

A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin

by Jinhee Hwang, Rekha Balakrishnan, Eunjin Oh, Rajakrishnan Veluthakal and Debbie C. Thurmond

Int. J. Mol. Sci. 2024, 25(1), 137; https://doi.org/10.3390/ijms25010137 - 21 Dec 2023

Cited by 2 | Viewed by 1443

Abstract

Diet-related lipotoxic stress is a significant driver of skeletal muscle insulin resistance (IR) and type 2 diabetes (T2D) onset. β₂-adrenergic receptor (β-AR) agonism promotes insulin sensitivity in vivo under lipotoxic stress conditions. Here, we established an in vitro paradigm of lipotoxic [...] Read more.

Diet-related lipotoxic stress is a significant driver of skeletal muscle insulin resistance (IR) and type 2 diabetes (T2D) onset. β₂-adrenergic receptor (β-AR) agonism promotes insulin sensitivity in vivo under lipotoxic stress conditions. Here, we established an in vitro paradigm of lipotoxic stress using palmitate (Palm) in rat skeletal muscle cells to determine if β-AR agonism could cooperate with double C-2-like domain beta (DOC2B) enrichment to promote skeletal muscle insulin sensitivity under Palm-stress conditions. Previously, human T2D skeletal muscles were shown to be deficient for DOC2B, and DOC2B enrichment resisted IR in vivo. Our Palm-stress paradigm induced IR and β-AR resistance, reduced DOC2B protein levels, triggered cytoskeletal cofilin phosphorylation, and reduced GLUT4 translocation to the plasma membrane (PM). By enhancing DOC2B levels in rat skeletal muscle, we showed that the deleterious effects of palmitate exposure upon cofilin, insulin, and β-AR-stimulated GLUT4 trafficking to the PM and glucose uptake were preventable. In conclusion, we revealed a useful in vitro paradigm of Palm-induced stress to test for factors that can prevent/reverse skeletal muscle dysfunctions related to obesity/pre-T2D. Discerning strategies to enrich DOC2B and promote β-AR agonism can resist skeletal muscle IR and halt progression to T2D. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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13 pages, 3106 KiB

Open AccessArticle

Circulating Levels of IL-8 and MCP-1 in Healthy Adults: Changes after an Acute Aerobic Exercise and Association with Body Composition and Energy Metabolism

by Rudite Lagzdina, Maija Rumaka, Gita Gersone and Peteris Tretjakovs

Int. J. Mol. Sci. 2023, 24(19), 14725; https://doi.org/10.3390/ijms241914725 - 29 Sep 2023

Cited by 1 | Viewed by 1191

Abstract

The most recent WHO recommendations about physical activity emphasise the importance of total exercise volume above the significance of the duration of each bout. This study examined whether acute aerobic exercise changes circulating levels of IL-8 and MCP-1 and if these changes are [...] Read more.

The most recent WHO recommendations about physical activity emphasise the importance of total exercise volume above the significance of the duration of each bout. This study examined whether acute aerobic exercise changes circulating levels of IL-8 and MCP-1 and if these changes are associated with body composition and energy metabolism. Healthy adult volunteers completed a 10 min walking–running exercise on a treadmill. Indirect calorimetry was used to determine their resting metabolic rate (RMR) and energy expenditure (EE) during the exercise. Pre-exercise levels of IL-8 and MCP-1 were similar in both sexes. There were positive correlations of pre-exercise IL-8 with body mass, waist circumference, and lean body mass in men and pre-exercise MCP-1 with RMR in women. The exercise led to an increase in IL-8 of 68% and a decrease in MCP-1 of 74% of participants. An increase in post-exercise IL-8 in men was associated with greater walking EE and a greater increase in walking EE. The increase in post-exercise MCP-1 was associated with a lower RMR and running EE in women. There are both sex and individual variations in changes in chemokine secretion in response to the same exercise situation and their associations with values of metabolic parameters. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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25 pages, 5032 KiB

Open AccessArticle

Reciprocal Regulation of Peroxisome Biogenesis and Myogenic Factors Is Critical for Myogenesis

by Chuan-Che Wu, Wei-Cheng Chen, Wen-Po Hsiao, Kai-Fan Huang, Yi-Shiuan Liao, Huang-Bin Lin, Yi-Ju Wu, Chien-Han Kao and Shen-Liang Chen

Int. J. Mol. Sci. 2023, 24(15), 12262; https://doi.org/10.3390/ijms241512262 - 31 Jul 2023

Cited by 3 | Viewed by 1643

Abstract

Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO [...] Read more.

Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO DNA, ROS level, and redox ratio increased in myotubes, but the membrane potential (Δψm) and ATP content reduced, implying that the MITO efficiency might reduce during myogenesis. The PEXO number and density both increased during myogenesis, which probably resulted from the accumulation and increased biogenesis of PEXO. The expression of PEXO biogenesis factors was induced during myogenesis in vitro and in utero, and their promoters were also activated by MyoD. Knockdown of the biogenesis factors Pex3 repressed not only the PEXO density and functions but also the levels of MITO genes and functions, suggesting a close coupling between PEXO biogenesis and MITO functions. Surprisingly, Pex3 knockdown by the CRISPRi system repressed myogenic differentiation, indicating critical involvement of PEXO biogenesis in myogenesis. Taken together, these observations suggest that the dynamics and functions of both MITO and PEXO are coupled with each other and with the metabolic changes that occur during myogenesis, and these metabolic couplings are critical to myogenesis. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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Review

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10 pages, 243 KiB

Open AccessReview

Recent Advances of Exosomes Derived from Skeletal Muscle and Crosstalk with Other Tissues

by Jia Luo, Qiang Pu and Xiaoqian Wu

Int. J. Mol. Sci. 2024, 25(20), 10877; https://doi.org/10.3390/ijms252010877 - 10 Oct 2024

Viewed by 1234

Abstract

Skeletal muscle plays a crucial role in movement, metabolism, and energy homeostasis. As the most metabolically active endocrine organ in the body, it has recently attracted widespread attention. Skeletal muscle possesses the ability to release adipocytokines, bioactive peptides, small molecular metabolites, nucleotides, and [...] Read more.

Skeletal muscle plays a crucial role in movement, metabolism, and energy homeostasis. As the most metabolically active endocrine organ in the body, it has recently attracted widespread attention. Skeletal muscle possesses the ability to release adipocytokines, bioactive peptides, small molecular metabolites, nucleotides, and other myogenic cell factors; some of which have been shown to be encapsulated within small vesicles, particularly exosomes. These skeletal muscle exosomes (SKM-Exos) are released into the bloodstream and subsequently interact with receptor cell membranes to modulate the physiological and pathological characteristics of various tissues. Therefore, SKM-Exos may facilitate diverse interactions between skeletal muscle and other tissues while also serving as biomarkers that reflect the physiological and pathological states of muscle function. This review delves into the pivotal role and intricate molecular mechanisms of SKM-Exos and its derived miRNAs in the maturation and rejuvenation of skeletal muscle, along with their intercellular signaling dynamics and physiological significance in interfacing with other tissues. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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34 pages, 1936 KiB

Open AccessReview

Advancements in Drug Delivery Systems for the Treatment of Sarcopenia: An Updated Overview

by Alfred Najm, Elena-Theodora Moldoveanu, Adelina-Gabriela Niculescu, Alexandru Mihai Grumezescu, Mircea Beuran and Bogdan Severus Gaspar

Int. J. Mol. Sci. 2024, 25(19), 10766; https://doi.org/10.3390/ijms251910766 - 7 Oct 2024

Viewed by 1178

Abstract

Since sarcopenia is a progressive condition that leads to decreased muscle mass and function, especially in elderly people, it is a public health problem that requires attention from researchers. This review aims to highlight drug delivery systems that have a high and efficient [...] Read more.

Since sarcopenia is a progressive condition that leads to decreased muscle mass and function, especially in elderly people, it is a public health problem that requires attention from researchers. This review aims to highlight drug delivery systems that have a high and efficient therapeutic potential for sarcopenia. Current as well as future research needs to consider the barriers encountered in the realization of delivery systems, such as the route of administration, the interaction of the systems with the aggressive environment of the human body, the efficient delivery and loading of the systems with therapeutic agents, and the targeted delivery of therapeutic agents into the muscle tissue without creating undesirable adverse effects. Thus, this paper sets the framework of existing drug delivery possibilities for the treatment of sarcopenia, serving as an inception point for future interdisciplinary studies. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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28 pages, 1656 KiB

Open AccessReview

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers

by David S. Kump

Int. J. Mol. Sci. 2024, 25(12), 6480; https://doi.org/10.3390/ijms25126480 - 12 Jun 2024

Viewed by 1769

Abstract

Skeletal muscle (SKM), despite comprising ~40% of body mass, rarely manifests cancer. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits the development of new cancer as well as negates potential metastasis to [...] Read more.

Skeletal muscle (SKM), despite comprising ~40% of body mass, rarely manifests cancer. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits the development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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17 pages, 1687 KiB

Open AccessReview

Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?

by Angelina Titova, Sergey Nikolaev, Airat Bilyalov, Nikita Filatov, Sergei Brovkin, Dmitrii Shestakov, Igor Khatkov, Ekaterina Pismennaya, Vyacheslav Bondarev, Margarita Antyuxina, Elena Shagimardanova, Natalia Bodunova and Oleg Gusev

Int. J. Mol. Sci. 2024, 25(9), 4985; https://doi.org/10.3390/ijms25094985 - 3 May 2024

Viewed by 2607

Abstract

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. [...] Read more.

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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23 pages, 1152 KiB

Open AccessReview

Disuse-Induced Muscle Fatigue: Facts and Assumptions

by Xenia V. Sergeeva, Irina D. Lvova and Kristina A. Sharlo

Int. J. Mol. Sci. 2024, 25(9), 4984; https://doi.org/10.3390/ijms25094984 - 3 May 2024

Cited by 2 | Viewed by 1755

Abstract

Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle [...] Read more.

Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, “oxidative“ “slow” phenotype to a “fast” “glycolytic“ one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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20 pages, 2419 KiB

Open AccessReview

Prediabetes-Associated Changes in Skeletal Muscle Function and Their Possible Links with Diabetes: A Literature Review

by Mandlakazi Dlamini and Andile Khathi

Int. J. Mol. Sci. 2024, 25(1), 469; https://doi.org/10.3390/ijms25010469 - 29 Dec 2023

Cited by 1 | Viewed by 2335

Abstract

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does [...] Read more.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes (PreDM) is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on PreDM is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as PreDM is a reversible condition if it is detected in the early stages. The literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes are not well elucidated. In this review, we seek to review the existing literature on PreDM- and T2DM-associated changes in skeletal muscle function. Full article

(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)

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