Human skeletal muscle biopsies from a 3h IL-6 infusion
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10685 | GEO | 2008/05/28
SECONDARY ACCESSION(S): PRJNA107675
REPOSITORIES: GEO
Similar Datasets
Project description:Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. Keywords: Human skeletal muscle time course response to IL-6 infusion IL-6 was infused for 3 h into healthy young males (n=7) and muscle biopsies obtained at time points 0, 3 and 6 h in these individuals. Affymetrix microarray analysis of gene expression profiling in muscle were carried out on 3 randomly chosen subjects.
2008-05-27 | E-GEOD-10685 | biostudies-arrayexpress
Project description:To identify insulin responsive genes in humans, in the first protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a two-hour of hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp. A variable infusion of glucose (180 g/l) enriched with tritiated glucose (100 μCi/500 ml) maintained euglycemia during insulin infusion, with monitoring of plasma glucose concentration every 5 to 10 min during the basal and clamp periods using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). In the second protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a 3-hour hyperinsulinemic (infusion rate 40 mU/m2/min) euglycemic clamp in order to increase the effects of insulin on gene expression. A variable infusion of glucose (180 g/l) was used to maintain euglycemia during insulin infusion with monitoring of plasma glucose concentration every 5 to 10 min using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). Keywords: dose response The muscle biopsies were obtained from the vastus lateralis muscle under local anesthesia before and after hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp
2007-03-01 | E-GEOD-7146 | biostudies-arrayexpress
Project description:To identify insulin responsive genes in humans, in the first protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a two-hour of hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp. A variable infusion of glucose (180 g/l) enriched with tritiated glucose (100 μCi/500 ml) maintained euglycemia during insulin infusion, with monitoring of plasma glucose concentration every 5 to 10 min during the basal and clamp periods using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). In the second protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a 3-hour hyperinsulinemic (infusion rate 40 mU/m2/min) euglycemic clamp in order to increase the effects of insulin on gene expression. A variable infusion of glucose (180 g/l) was used to maintain euglycemia during insulin infusion with monitoring of plasma glucose concentration every 5 to 10 min using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). Keywords: dose response
2007-03-01 | GSE7146 | GEO
Project description:Physical exercise training is associated with increased glucose uptake in skeletal muscle and improved glycemic control. Histone Deacetylases (HDACs) are divided into three structurally defined subclasses and are critical for transcriptional regulation, cell cycle progression, and developmental events. HDAC5, a class IIa histone deacetylase regulates transcription of the insulin-responsive glucose transporter GLUT4 in cultured muscle cells. Interleukin-6 (IL-6) is a prototypical cytokine featuring functional redundancy and pleiotropy. Under healthy conditions the serum level of IL-6 is less than 4 pg/ml. The cytokine IL-6 was the first myokine found to be secreted into bloodstream in response to muscle contractions. Exercise intervention induce secretion of muscle-derived IL-6, leading to an acute and rebuses increase of systemic IL-6 up to 100-fold higher than basal levels a far greater increase than that of any other cytokine that has been measured. HDAC5 depletion in skeletal muscle lead to increased glucose uptake that was driven by IL-6 and p-AKT signaling. We specifically revealed that HDAC5 binds to the IL-6 promoter to regulate its transcription. These effects were facilitated by exercise and muscle contractions. In summary, we identified HDAC5 as a negative regulator of IL-6 synthesis and release in skeletal muscle. HDAC5 may exert beneficial effects through two different mechanisms, transcriptional control of genes required for glucose disposal and utilization, and HDAC5-dependent IL-6 signaling in order to improve glucose uptake in muscle in response to exercise.
2020-10-02 | GSE150485 | GEO
Project description:The discovery of novel exercise-regulated circulatory factors has fueled interest in the role of organ-crosstalk, especially between skeletal muscle and adipose tissue in mediating beneficial effects of exercise. We studied the adipose tissue transcriptome in men and women with normal glucose tolerance or type 2 diabetes following an acute exercise bout, revealing substantial exercise and time-dependent changes, and a sustained increase in inflammatory genes unique to Type 2 diabetes. We identify Oncostatin-M as one of the most upregulated adipose tissue secreted factors post exercise. In cultured human adipocytes, oncostatin-M enhanced MAPK signalling and regulates lipolysis. Oncostatin-M expression predominantly arises from adipose tissue immune cell fractions, while the corresponding receptors are expressed in adipocytes. Oncostatin-M expression is induced in cultured human Thp1 macrophages in response to exercise-like stimuli. Our results suggest immune cells, via secreted factors such as oncostatin-M, are important in crosstalk between skeletal muscle and adipose tissue during exercise, to regulate adipocyte metabolism and adaptation.
2023-11-21 | GSE198922 | GEO
Project description:Human skeletal muscle biopsies from a 3h IL-6 infusion
| PRJNA107675 | ENA
Project description:Exercise triggers skeletal muscle signalling pathways that modulate the release of circulating factors to cause systemic health benefits. Understanding these mechanisms could lead to better strategies for treating cardiometabolic diseases. We previously showed that acute exercise induces >1000 changes in protein phosphorylation in human muscle. Here we employed a strategy to deconvolute this network by analysing phosphoproteomes of rat L6 myotubes treated with small molecules that mimic different aspects of exercise signalling. Bioinformatics suggested that combining β-adrenergic and calcium agonists would yield a phosphoproteome most closely resembling exercise. Experimental analysis supported this but also revealed a surprising divergence in signalling from that observed with either drug alone. Dual stimulation promoted multisite phosphorylation of SERBP1, a regulator of Serpine1 mRNA stability, a pro-thrombotic fibrotic secreted protein. Secretomic analysis of L6 myotubes treated with β-adrenergic and calcium agonists revealed a significant decrease in SERPINE1 secretion and other deleterious secretory factors. This provides a novel approach to dissect the beneficial effects of exercise and demonstrates an underappreciated effect of exercise to reduce the circulating levels of certain factors, providing new insights into exercise benefits and their therapeutic potential.
2019-09-26 | PXD014322 | Pride
Project description:Appropriate amount of exercise is the best way to prevent various diseases and have a healthy life. Skeletal muscles communicate with other organs through myokines, which are secreted by muscle itself during exercise and elicit various effects in the body. However, despite the years of efforts to understand molecular mechanisms of crosstalk between muscle and other organs that mediate the beneficial effects of exercise are not completely understood. To identify novel myokines, we used an in vitro exercise model in C2C12 cells using the electrical pulse stimulation (EPS) that can mimic muscle contraction. We generated RNA-seq data of seven in vitro samples to costruct a prediction model based on differentially expressed genes, showing significantly mimicking in vivo exercise.
2022-12-14 | GSE176563 | GEO
Project description:Exercise affects the expression of microRNAs (miR/s) and muscle-derived extracellular vesicles (EVs). To evaluate sarcoplasmic and secreted miR expression in human skeletal muscle in response to exercise-mimetic contractile activity, we utilized a three-dimensional tissue-engineered model of human skeletal muscle (“myobundles”). Myobundles were subjected to three culture conditions: no electrical stimulation (CTL), chronic low frequency stimulation (CLFS), or intermittent high frequency stimulation (IHFS) for 7 days. RNA was isolated from myobundles and from extracellular vesicles (EVs) secreted by myobundles into culture media; miR abundance was analyzed by miRNA-sequencing. We used edgeR and a within-sample design to evaluate differential miR expression and Pearson correlation to evaluate correlations between myobundle and EV populations within treatments with statistical significance set at p<0.05. Numerous miRs were differentially expressed between myobundles and EVs; 116 miRs were differentially expressed within CTL, 3 within CLFS, and 2 within IHFS. Additionally, 25 miRs were significantly correlated (18 in CTL, 5 in CLFS, 2 in IHFS) between myobundles and EVs. Electrical stimulation resulted in differential expression of 8 miRs in myobundles and only 1 miR in EVs. Several KEGG pathways, known to play a role in regulation of skeletal muscle, were enriched, with differentially overrepresented miRs between myobundle and EV populations identified using miEAA. Together, these results demonstrate that in vitro exercise-mimetic contractile activity of human engineered muscle affects both their expression of miRs and number of secreted EVs. These results also identify novel miRs of interest for future studies of the role of exercise in organ-organ interactions in vivo
2022-09-28 | GSE203157 | GEO
Project description:Background
Loss of skeletal muscle mass in cancer cachexia is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are not yet clearly defined. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in the putative muscle secretome associated with cancer-induced cachexia to gain a better understanding of cellular mechanisms involved and to identify secreted proteins which might reflect this wasting process.
Methods
We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were then submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Multiple reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Finally, we investigated the regulation of the production of these secreted proteins by muscle in vitro and in vivo.
Results
Our results revealed a dramatic increased muscular production (2-to 25-fold) of several acute phase reactants (APR: haptoglobin, serpina3n, complement C3, serum amyloid A1) which are released in the circulation during C26 cancer cachexia. This observation was confirmed in two other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Our results showed also that IL-6 plays a major role in the muscular induction of these APR in vivo, while glucocorticoids and pro-inflammatory cytokines stimulate directly their increased expression in muscle cells in vitro.
Conclusions
Muscle wasting caused by cancer is associated with marked changes in muscle secretome. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.
2021-01-24 | PXD019433 | panorama