Search Results (292)

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Background/Objectives: Diagnosis of Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) currently lacks objective biomarkers. Therefore, this retrospective study aimed to investigate differences in glucose metabolism in the axial musculoskeletal system in PSPS-T2 patients by means of [¹⁸F]FDG PET-CT imaging. Methods: Nine PSPS-T2 patients (five females, four males; mean age of 53 ± 4.82 years) and nine age- and gender-matched healthy controls (five females, four males; mean age of 53 ± 3.91 years) were included. For each participant, 24 regions of interest (ROIs) were manually drawn, including areas of the vertebral endplates, the intervertebral discs, and the psoas muscles. For each ROI, the mean standardized uptake values (SUVs) were assessed. Group differences were evaluated using repeated measures ANOVA with Bonferroni-adjusted post-hoc pairwise comparisons. Additionally, Pearson correlation analyses examined associations between SUV_mean values and the Numerical Rating Scale (NRS) pain scores. Results: Results demonstrated significantly higher SUV_mean values in healthy controls compared to PSPS-T2 patients, particularly at the superior endplates of L4 and S1, the intervertebral discs at L4-L5 and L5-S1, and the posterior endplates of L4 and L5. Although PSPS-T2 patients exhibited higher SUV_mean values than controls in the psoas muscle, these differences were not statistically significant. Additionally, no significant correlations were found between SUV_mean values and NRS pain scores, suggesting that metabolic activity alone does not directly reflect pain severity. Conclusions: Despite the limited sample size of this pilot study, the metabolic fingerprint of the axial musculoskeletal system was shown to be distinctly different in PSPS-T2 patients compared to healthy controls. This could lead to an improved understanding of PSPS-T2 pathophysiology and might open new doors for better diagnosis and treatment strategies. Full article

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

Background/Objectives: Myogenesis, the process by which myoblasts differentiate into multinucleated muscle fibers, is tightly regulated by transcription factors, signaling pathways, and metabolic cues. Among these, fatty acids have emerged as key regulators beyond their traditional role as energy substrates. Oleic acid, a monounsaturated fatty acid, has been shown to modulate muscle differentiation, potentially influencing myogenic pathways. This study examines the role of oleic acid in promoting C2C12 myoblast differentiation and its associated molecular mechanisms, comparing it to standard horse serum (HS)-based differentiation protocols. Methods: C2C12 murine myoblasts were cultured under proliferative conditions and differentiated using DMEM supplemented with either 2% HS or oleic acid (C18:1, n-9). The molecular signaling pathway was evaluated by measuring the expression of p38 MAPK, β-catenin, GLUT4, and NDRG1. Results: Oleic acid promoted the differentiation of C2C12 cells, as evidenced by a progressively elongated morphology, as well as the induction of muscle-specific myogenin, myosin heavy chain (MHC), and MyoD. Moreover, oleic acid reduced the expression of Atrogin-1 and MuRF1 ubiquitin E3 ligase. BODIPY staining revealed the enhanced accumulation of lipid droplets in oleic acid-treated cells. The Western blot analysis demonstrated robust activation of p38 MAPK and β-catenin pathways in response to oleic acid, compared with HS. Additionally, oleic acid upregulated GLUT4 expression and increased the phosphorylation of insulin receptor and NDRG1, indicating an enhanced glucose uptake capacity. Conclusions: These findings demonstrate that oleic acid promotes C2C12 myoblast differentiation and improves glucose uptake via GLUT4. Oleic acid emerges as a promising metabolic regulator of myogenesis, offering potential therapeutic applications for muscle regeneration in muscle-related pathologies. Full article

Aging is a significant risk factor for various conditions, including neurodegeneration, cardiovascular disease, and type 2 diabetes. The accumulation of reactive oxygen species (ROS) and a decline in antioxidant defense are mechanisms that are widely acknowledged as causing the acceleration of both aging and the onset of age-related diseases. To promote longevity and reduce the risk of the development of aging-related disorders, it is essential to prevent or minimize oxidative stress and enhance antioxidant defense. It has been shown that Anoectochilus burmannicus (AB), a jewel orchid rich in phenolic compounds, can impact various biological activities associated with aging prevention. These activities include antioxidant, anti-inflammation, anti-insulin resistance, and anti-obesity effects. The aim of this study was to explore whether AB extract (ABE) could serve as an anti-aging agent using a Sod1-deficient Drosophila model, which accelerates the process of aging through ROS production. The results demonstrated that ABE, at a concentration of 2.5 mg/mL, significantly extended the lifespan of the flies and helped maintain their locomotor activity as they aged. ABE also reduced the age-related accumulation of damaged proteins in the muscle of the flies by inhibiting the expression of Gstd1, a genetic marker for oxidative stress. This finding agrees with those from in vitro experiments, which have shown the potential for ABE to reduce the production of ROS induced by H₂O₂ in myoblasts. ABE has been shown to attenuate insulin resistance, an age-related disorder, by inhibiting the pro-inflammatory cytokine TNF-α, which in turn increased insulin-stimulated glucose uptake in adipocytes. These findings suggest a promising role of ABE as an ingredient in functional foods or nutraceuticals aimed at promoting health, preventing oxidative stress, and potentially managing age-associated diseases. Full article

N-acetylaspartate (NAA) is the second most abundant metabolite in the human brain. Quantifiable amounts of NAA are also present in the blood, but its role in the peripheral tissues is largely unknown. First, we determined the acute effects of insulin administration on NAA concentrations; second, we assessed whether circulating NAA levels associate with markers of central and peripheral insulin sensitivity. A total of 24 persons living with obesity and 19 healthy, lean controls, without neurological disorders, underwent a euglycemic hyperinsulinemic clamp combined with fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET) imaging of the brain, abdomen, and femoral area. Plasma concentrations of NAA were measured at baseline and ~2 h into the clamp using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS-MS). Glucose uptake (GU) rates were analysed using a fractional uptake rate. Serum acetate levels were also assessed using nuclear magnetic resonance (NMR) metabolomics. From baseline to steady-state, insulin levels increased from a mean level of 66 to 447 pmol/L (p < 0.0001). Over this period, circulating NAA concentrations decreased by 5% (p = 0.01), similarly in both groups. The change in NAA was inversely related with the change in plasma acetate (r = −0.36, p = 0.048). Circulating NAA was associated with waist–hip ratio (rho = −0.54, p = 0.0002), steady-state free fatty acids (rho = −0.44, p = 0.003), and directly with HDL cholesterol (rho = 0.54, p = 0.0002), adiponectin (rho = 0.48, p = 0.003), and whole-body insulin sensitivity (rho = 0.34, p = 0.03). Circulating NAA was directly related with skeletal muscle (rho = 0.42, p = 0.01) and visceral adipose tissue GU (rho = 0.41, p = 0.02). Insulin administration leads to a small decrease in circulating NAA levels, and NAA associates consistently with markers of insulin sensitivity. While plasma NAA may be relevant to aspects of whole-body homeostasis, mechanistic insights are needed. Full article

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, especially in regions like Eastern Europe, South Asia, and Latin America. A significant portion of these cases (80%) is linked to atherosclerosis, which can lead to severe conditions like ischemic heart disease and stroke, with atherosclerosis (ATS) responsible for the majority of cases. This review explores the multifaceted relationship between insulin resistance (IR) and ATS, highlighting their roles as both independent and interrelated contributors to cardiovascular risk. ATS is characterized by lipid accumulation and chronic inflammation within arterial walls, driven by factors such as hypertension, dyslipidemia, and genetic predisposition, with endothelial dysfunction as a key early event. The early detection of subclinical ATS is critical and can be achieved through a combination of non-invasive imaging techniques—such as coronary artery calcium scoring and carotid ultrasound—and comprehensive risk profiling. IR, marked by impaired glucose uptake in liver, muscle, and adipose tissue, often precedes early diabetes and is associated with metabolic disturbances, including dyslipidemia and chronic inflammation. The diagnosis of IR relies on surrogate indices such as HOMA-IR, the QUICKI, and the TyG index, which facilitate screening in clinical practice. Compelling evidence indicates that IR independently predicts the progression of atherosclerotic plaques, even in non-diabetic individuals, and operates through both traditional risk factors and direct vascular effects. Understanding and targeting the IR–ATS axis is essential for the effective prevention and management of cardiovascular disease. Full article

Background/Objectives: Dietary supplementation with medium-chain triglycerides (MCTs) improves walking balance and cognitive function in healthy older adults. This study aimed to determine the biological effects of MCTs on gait-related skeletal muscles in healthy older adults by analyzing muscle density and glucose metabolism. Methods: ¹⁸F-FDG-PET/CT imaging data from 63 participants (18 g/day of MCTs and matching placebo in the form of a jelly stick [6 g each, ingested 3 times/day]) in a randomized clinical trial were analyzed. The three-dimensional regions of interest were set as muscles associated with walking balance (bilateral triceps, psoas, and vastus medialis). Each muscle’s mean standardized uptake value (SUV_mean) and Hounsfield units (HU) were calculated for relative quantitative measurements. Results: MCT supplementation for 3 months decreased the SUV_mean (p < 0.001) and increased the HU of the psoas (r = −0.61) and vastus medialis muscles (r = −0.59) (p < 0.001); no changes were apparent in participants supplemented with long-chain triglycerides. The changes in the SUV_mean for each muscle were correlated negatively with those of plasma β-hydroxybutyrate in MCT-supplemented participants (r = −0.57 [psoas] and −0.59 [vastus medialis]; p < 0.001). Conclusion: A 3-month MCT supplementation suppressed glucose metabolism and increased the muscle density in gait-related skeletal muscles, consistent with previous findings that MCT supplementation stabilizes balance functions during walking in healthy older adults. Full article

Background: Dietary consumption of insulinogenic amino acids (IAA) is known to contribute to the development of insulin resistance. It remains to be studied whether dietary IAA restriction improves glucose metabolism and insulin sensitivity and whether this improvement is related to alterations in glucose metabolism in peripheral tissues. The objective of this study was to examine the effect of IAA restriction on glucose metabolism in a piglet model. Methods: Following the acclimation period, thirty-two seven-day-old male piglets were randomly assigned into one of three groups for three weeks as follows (n = 10–11/group): (1) NR (control): basal diet without IAA restriction; (2) R50: basal diet with IAA restricted by 50%; (3) R75: basal diet with IAA restricted by 75%. IAA were alanine (Ala), arginine (Arg), isoleucine (Ile), leucine (Leu), lysine (Lys), threonine (Thr), phenylalanine (Phe), and valine (Val) as suggested by previous studies. Thermal images, body weight, and growth parameters were recorded weekly, oral glucose tolerance tests were performed on week 2 of the study, and blood and tissue samples were collected on week 3 after a meal test. Results: R75 improved glucose tolerance and, together with R50, reduced blood insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) value, which is suggestive of improved insulin sensitivity following IAA restriction. R75 increased thermal radiation and decreased adipocyte number in white adipose tissue (WAT). R75 had a greater transcript of glucose transporter 1 (GLUT1), phosphofructokinase, liver type (PFKL), and pyruvate kinase, liver, and RBC (PKLR) in the liver and glucokinase (GCK) in WAT indicating a higher uptake of glucose in the liver and greater glycolysis in both liver and WAT. R75 increased the mRNA abundance of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT1) in skeletal muscle suggestive of enhanced insulin signaling. Further, R75 had a higher mRNA of fibroblast growth factor 21 (FGF-21) in both the liver and hypothalamus and its upstream molecules such as activating transcription factor 4 (ATF4) and inhibin subunit beta E (INHBE) which may contribute to increased energy expenditure and improved glucose tolerance during IAA restriction. Conclusions: IAA restriction improves glucose tolerance and insulin sensitivity in piglets while not reducing body weight, likely through improved hepatic glycolysis and insulin signaling in skeletal muscle, and induced FGF-21 signaling in both the liver and hypothalamus. Full article

Background/Objectives: Athletic performance matters for athletes and fitness enthusiasts. Scientific dietary intervention may boost athletic performance alongside training. Intermittent fasting, like time-restricted fasting (TF), may enhance metabolic health. NAD⁺ supplement nicotinamide mononucleotide (NMN) improves mitochondrial activity. Both potentially boost athletic performance. However, whether TF combined with NMN treatment can further enhance athletic ability is unclear. Methods: Healthy Kunming mice were utilized to test the effects of NMN and TF on the athletic performance of mice. To simulate the in vivo state and further verify the role of TF and NMN, low glucose combined with NMN was used to intervene in C2C12 cells. The exercise capacity of mice was evaluated through motor behavior experiments. At the same time, blood gas analysis and kit tests were used to assess oxygen uptake capacity and post-exercise oxidative stress levels. Muscle development and mitochondrial function were examined through gene expression, protein analysis, and enzyme activity tests, and the distribution of intestinal microbiota and short-chain fatty acid content were also analyzed. Results: The results show that TF combined with NMN improved mitochondrial dynamics and biosynthesis, mitochondrial respiratory function, and oxidative metabolism. Then, the intervention enhanced mice’s endurance, limb strength, motor coordination, and balance and reduced oxidative damage after exercise. Moreover, TF combined with NMN significantly increased the gut microbiota diversity and upregulated Ruminococcus, Roseburia, and Akkermansia in intestinal bacteria and short-chain fatty acids, which are associated with athletic performance. Conclusion: TF combined with NMN enhanced mitochondrial function, improved energy metabolism, modulated the gut microbiota and short-chain fatty acids, and affected muscle fiber transformation, ultimately leading to an overall improvement in exercise performance. These findings provide a theoretical framework for expanding the application of NMN and TF in kinesiology. Full article

Background: Phytochemicals possess diverse therapeutic potential; however, the impact of arene substitutions on the pharmacological properties of the bibenzyl compounds batatasin III and gigantol, derived from Dendrobium venustum, remains unexplored. Objectives: This study examines how structural differences between these compounds affect cellular glucose uptake and lipid metabolism during adipocyte differentiation. Methods: The effects of both bibenzyl compounds on cytotoxicity and glucose uptake were assessed in mouse and human pre-adipocytes and rat skeletal muscle myoblasts using colorimetric assays. Lipid metabolism was evaluated through Oil Red O staining and quantification of triglyceride and glycerol levels, while protein and gene expression during adipocyte differentiation were analyzed via western blotting and RT-qPCR. Results: At the highest non-cytotoxic concentration (25 µM), gigantol significantly enhanced glucose uptake (up to 2-fold) under both basal and insulin-stimulated conditions, whereas batatasin III showed a similar effect only under basal conditions. Gigantol upregulated GLUT1 and GLUT4 in myotubes but downregulated them in adipocytes, whereas batatasin III had minimal impact on these transporters. Both compounds suppressed lipid accumulation in mouse and human adipocytes by decreasing intracellular triglyceride content and promoting extracellular glycerol release. However, batatasin III did not affect extracellular glycerol release during early adipocyte differentiation, as evidenced by the marked downregulation of key lipogenic proteins (PLIN1, LPL, FABP4) observed only with gigantol. Molecular docking analyses suggest that gigantol’s greater bioactivity may result from its higher number of arene substitutions. Conclusions: This study provides the first evidence that differences in arene substitutions among orchid-derived bibenzyls influence their pharmacological properties. Our findings support the strategic modification of natural products as a potential approach for managing metabolic disorders. Full article

Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), impairing insulinotropic effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), impair insulin receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. β-cell dysfunction in GDM is associated with decreased pancreatic duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), and mitochondrial dysfunction leading to impaired ATP production and reduced glucose-stimulated insulin secretion. Excessive gestational weight gain exacerbates insulin resistance through hyperleptinemia, which downregulates insulin receptor expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation in skeletal muscle, impairing GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids which activate protein kinase C, inhibiting insulin signaling. Placental 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) overactivity elevates cortisol levels, which activate glucocorticoid receptors to further reduce insulin sensitivity. GDM diagnostic thresholds (≥92 mg/dL fasting, ≥153 mg/dL post-load) are lower than type 2 diabetes to prevent fetal hyperinsulinemia and macrosomia. Management strategies focus on lifestyle modifications, including dietary carbohydrate restriction and exercise. Pharmacological interventions, such as insulin or metformin, aim to restore AMPK signaling and reduce hepatic glucose output. Emerging therapies, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, show potential in improving glycemic control and reducing inflammation. A mechanistic understanding of GDM pathophysiology is essential for developing targeted therapeutic strategies to prevent both adverse pregnancy outcomes and the progression to overt diabetes in affected women. Full article

Exercise plays a crucial role in maintaining metabolic health, enhancing muscle function, and improving insulin sensitivity, thereby preventing metabolic diseases such as type 2 diabetes. Emerging evidence highlights the significance of the cystathionine γ-lyase (CSE)/hydrogen sulfide (H₂S) signaling pathway as a pivotal regulator in the molecular and physiological adaptations induced by exercise. This review comprehensively examines the biosynthesis and metabolism of H₂S, its distribution in different muscle tissues, and the mechanisms by which CSE/H₂S influences muscle contraction, repair, and protein synthesis. Additionally, it explores how CSE/H₂S modulates insulin signaling pathways, glucose uptake, and lipid metabolism, thereby enhancing insulin sensitivity. The potential of H₂S donors as exercise supplements is also discussed, highlighting their ability to improve exercise performance and metabolic health. Current research advancements, including the application of multi-omics approaches, are reviewed to provide a deeper understanding of the complex molecular networks involved. Furthermore, the challenges and future directions in CSE/H₂S research are addressed, emphasizing the need for further mechanistic studies and clinical applications. This review underscores the therapeutic potential of targeting the CSE/H₂S pathway to optimize the benefits of exercise and improve metabolic health. Full article

Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([¹⁸F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [¹⁸F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [¹⁸F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [¹⁸F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [¹⁸F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [¹⁸F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [¹⁸F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland–Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [¹⁸F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [¹⁸F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [¹⁸F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUV_peak are recommended for quantitative assessment. High [¹⁸F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles. Full article