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Schematic diagram of skeletal muscle fiber type differentiation during embryogenesis. Sox6 functions as a suppressor of slow fiber-specific genes and Six1/4 function as activators of fast fiber-specific genes. An arrow indicates activation and a bar with a horizontal line indicates suppression.
Source publication
The primary deficiency underlying metabolic syndrome is insulin resistance, in which insulin-responsive peripheral tissues fail to maintain glucose homeostasis. Because skeletal muscle is the major site for insulin-induced glucose uptake, impairments in skeletal muscle’s insulin responsiveness play a major role in the development of insulin resista...
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Myostatin was identified more than 20 years ago as a negative regulator of muscle mass in mice and cattle. Since then, a wealth of studies have uncovered the potential involvement of myostatin in muscle atrophy and sparked interest in myostatin as a promising therapeutic target to counteract decline of muscle mass in patients afflicted with differe...
To examine the effect of acute and chronic exercise on adipose tissue GLUT4 expression, a total of 20 healthy, male subjects performed one of two studies. Ten subjects performed cycle ergometer exercise for 60 min at 73 ± 2% VO2 peak and abdominal adipose tissue samples were obtained immediately before and after exercise and after 3 h of recovery....
Citations
... When the body absorbs energy and converts it into glucose, activation of the Akt signaling pathway further regulates the translocation of glucose transporter 4 (GLUT4) from the internal compartment to the plasma membrane of skeletal muscles [7]. Insulin may stimulate glucose transport over the plasma membrane, where approximately 85% of glucose 2 of 17 absorption is dependent on GLUT4 [8]. Previous research indicates that the decline in ability of the transport capacity of GLUT4 may result in a reduction in glycogen synthesis, which is likely to be one of the important reasons contributing to the development of insulin resistance in skeletal muscle [9]. ...
In this study, we aimed to explore the potential targets and functional mechanisms of Rk1 combined with Rg5 (Rk1+Rg5) against type II diabetes mellitus (T2DM). Network pharmacology and molecular docking were used to predict and verify the targets and signaling pathways of Rk1+Rg5 against T2DM. The results were further confirmed by a db/db mouse model and a model using PA-induced L6 cells. According to network pharmacology, a total of 250 core targets of Rk1+Rg5 towards T2DM were identified; the insulin resistance signaling pathways were enriched by KEGG. Results of molecular docking indicated good binding affinity of Rk1 and Rg5 to Akt1. In vivo and in vitro studies further showed that Rk1+Rg5 is an inhibitor of skeletal muscle insulin resistance. The results showed that Rk1+Rg5 significantly improved the hyperglycemic state of db/db mice, alleviated dyslipidemia, and promoted skeletal muscle glucose uptake. This phenomenon was closely related to the alleviation of the insulin resistance in skeletal muscles. Finally, the combination activated the Akt signaling pathway and promoted GLUT4 translocation to the cell membrane for glucose uptake. Altogether, our findings, for the first time, demonstrate that the combination of Rk1 and Rg5 could be beneficial for anti-T2DM, possibly involving ameliorated insulin resistance.
... The integrative physiology of IR is mainly attributed to the defective insulin action at peripheral target tissues (skeletal muscle, liver, and adipose tissue). Among them, skeletal muscle, a vital organ for glucose clearance, taking charge of clearing approximately 75%-80% of postprandial glucose uptake and 95% of glucose uptake under hyperglycemia (Hagiwara, 2014), is deemed as the primary driver for the development of systemic IR (Carnagarin et al., 2015;Merz and Thurmond, 2020;Pyun et al., 2021). Consequently, remediating IR in skeletal muscle alone is sufficient to maintain systemic glucose homeostasis (Abdul-Ghani and DeFronzo, 2010;Merz and Thurmond, 2020). ...
Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.
... These outcomes have immediate implications for neonatal morbidity and mortality [62,63], but are also now recognized as setting the stage for an increased risk of metabolic dysregulations and metabolic syndrome (MetS) later in life [19,[64][65][66]. Central to MetS is muscle dysfunction, and in particular, muscle insulin sensitivity and metabolic function [67]. In addition, IUGR resulting in low birth weight (LBW) is now PGC-1α and PPARα are well-known transcription factors that regulate aspects of mitochondrial lipid oxidation. ...
... These outcomes have immediate implications for neonatal morbidity and mortality [62,63], but are also now recognized as setting the stage for an increased risk of metabolic dysregulations and metabolic syndrome (MetS) later in life [19,[64][65][66]. Central to MetS is muscle dysfunction, and in particular, muscle insulin sensitivity and metabolic function [67]. In addition, IUGR resulting in low birth weight (LBW) is now recognized as a central programming factor in lifelong impairments in muscle development and metabolism [24]. ...
Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload.
... The population of the COX deficient fibres was significantly higher in Ts1Cje male mice as compared with the WT male mice and the result of this study further supported the general understanding of the mitochondrial defects in individuals with DS [43][44][45][46]. A defective mitochondrial function in the quadriceps of individuals with DS was found in vivo [46] and the expression of COX2 protein was also found to be significantly lower in the soleus of Ts65Dn mice [42]. ...
Background
Down syndrome (DS) is a genetic disorder caused by presence of extra copy of human chromosome 21. It is characterised by several clinical phenotypes. Motor dysfunction due to hypotonia is commonly seen in individuals with DS and its etiology is yet unknown. Ts1Cje, which has a partial trisomy (Mmu16) homologous to Hsa21, is well reported to exhibit various typical neuropathological features seen in individuals with DS. This study investigated the role of skeletal muscles and peripheral nerve defects in contributing to muscle weakness in Ts1Cje mice.
Results
Assessment of the motor performance showed that, the forelimb grip strength was significantly (P<0.0001) greater in the WT mice compared to Ts1Cje mice regardless of gender. The average survival time of the WT mice during the hanging wire test was significantly (P<0.0001) greater compared to the Ts1Cje mice. Also, the WT mice performed significantly (P<0.05) better than the Ts1Cje mice in the latency to maintain a coordinated motor movement against the rotating rod. Adult Ts1Cje mice exhibited significantly (P<0.001) lower nerve conduction velocity compared with their aged matched WT mice. Further analysis showed a significantly (P<0.001) higher population of type I fibres in WT compared to Ts1Cje mice. Also, there was significantly (P<0.01) higher population of COX deficient fibres in Ts1Cje mice. Expression of Myf5 was significantly (P<0.05) reduced in triceps of Ts1Cje mice while MyoD expression was significantly (P<0.05) increased in quadriceps of Ts1Cje mice.
Conclusion
Ts1Cje mice exhibited weaker muscle strength. The lower population of the type I fibres and higher population of COX deficient fibres in Ts1Cje mice may contribute to the muscle weakness seen in this mouse model for DS.
Regulation of skeletal muscle blood flow is a complex process, which involves an integration of multiple mechanisms and a number of vasoactive compounds. Skeletal muscle blood flow may be affected by changes in microvascular structure or function which occur in pathological conditions such as hypertension with subsequent increase in vascular resistance. Exercise training may elicit beneficial effects on skeletal muscle blood flow by inducing favorable microvascular remodeling, capillary angiogenesis, and modulating vasomotor reactivity of small arteries and arterioles. In particular, activation of angiogenic process, with increase in capillary network, seems to have the major influence in ameliorating local blood flow in several tissues including skeletal muscle. Furthermore, phenotypic expression of skeletal muscle fiber type also has powerful influences on vascular structure and function in skeletal muscle, which may influence training-induced vascular adaptations in skeletal muscle. Recently, new approaches in exercise training have highlighted the key role of miRNAs in the modulation of hypertension.KeywordsMicrocirculationPhysical exerciseHypertensionCapillaries small resistance arteries
Background and aims
Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been suggested that some of these risk factors can have detrimental effects on the skeletal muscle while others can be a direct result of skeletal muscle abnormalities, showing a two-way directionality in the pathogenesis of the condition. This review aims to explore this bidirectional correlation by discussing the impact of metabolic syndrome on skeletal muscle tissue in general and will also discuss ways in which skeletal muscle alterations may contribute to the pathogenesis of metabolic syndrome.
Methods
Literature searches were conducted with key words (e.g. metabolic syndrome, skeletal muscle, hyperglycemia) using PubMed, EBSCOhost, Science Direct and Google Scholar. All article types were included in the search.
Results
The pathological mechanisms associated with metabolic syndrome, such as hyperglycemia and inflammation, have been associated with changes in skeletal muscle fiber composition, metabolism, insulin sensitivity, mitochondrial function, and strength. Additionally, some skeletal muscle alterations, particularly mitochondrial dysfunction and insulin resistance, are suggested to contribute to the development of metabolic syndrome. For example, the suggested underlying mechanisms of sarcopenia development are also contributors to metabolic syndrome pathogenesis.
Conclusion
Whilst numerous studies have identified a relationship between metabolic syndrome and skeletal muscle abnormalities, further investigation into the underlying mechanisms is needed to elucidate the best prevention and management strategies for these conditions.
The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes.
