Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA126135 | ENA |
REPOSITORIES: ENA
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Project description:Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta-cell dysfunction. In high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, and glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potentially important in the pathogenesis of DM, we analyzed gene expression in skeletal muscle from healthy metabolically characterized nondiabetic (family history negative and positive for DM) and diabetic Mexican-American subjects. We demonstrate that insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function. While NRF-1 expression is decreased only in diabetic subjects, expression of both PPARg coactivator 1-alpha and -beta (PGC1-a/PPARGC1, and PGC1-b/PERC), coactivators of NRF-1 and PPARg-dependent transcription, is decreased in both diabetic subjects and family history positive nondiabetic subjects. Decreased PGC1 expression may be responsible for decreased expression of NRFdependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM. Human muscle samples were obtained from five subjects with type 2 diabetes and ten subjects without diabetes, as well as 5 aliquots from a single subject without diabetes. The subjects without diabetes were further classified as family history positive (four subjects) or family history negative (six subjects).
2010-04-27 | E-GEOD-21340 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta-cell dysfunction. In high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, and glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potentially important in the pathogenesis of DM, we analyzed gene expression in skeletal muscle from healthy metabolically characterized nondiabetic (family history negative and positive for DM) and diabetic Mexican-American subjects. We demonstrate that insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function. While NRF-1 expression is decreased only in diabetic subjects, expression of both PPARg coactivator 1-alpha and -beta (PGC1-a/PPARGC1, and PGC1-b/PERC), coactivators of NRF-1 and PPARg-dependent transcription, is decreased in both diabetic subjects and family history positive nondiabetic subjects. Decreased PGC1 expression may be responsible for decreased expression of NRFdependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM.
2007-06-28 | E-CBIL-28 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta-cell dysfunction. In high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, and glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potentially important in the pathogenesis of DM, we analyzed gene expression in skeletal muscle from healthy metabolically characterized nondiabetic (family history negative and positive for DM) and diabetic Mexican-American subjects. We demonstrate that insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function. While NRF-1 expression is decreased only in diabetic subjects, expression of both PPARg coactivator 1-alpha and -beta (PGC1-a/PPARGC1, and PGC1-b/PERC), coactivators of NRF-1 and PPARg-dependent transcription, is decreased in both diabetic subjects and family history positive nondiabetic subjects. Decreased PGC1 expression may be responsible for decreased expression of NRFdependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM.
2010-04-14 | GSE21340 | GEO
Project description:Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) and is even present in offspring of diabetic parents. However, molecular mediators of insulin resistance remain unclear. We find that the top-ranking gene set in expression analysis of muscle from humans with T2D and normoglycemic insulin resistant subjects with parental family history (FH+) of T2D is increased expression of actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator MKL1. Furthermore, the SRF activator STARS is upregulated in FH+ and T2D and inversely correlated with insulin sensitivity. These patterns are recapitulated in insulin resistant mice, and linked to alterations in two other regulators of this pathway: reduced G-actin and increased nuclear localization of MKL1. Both genetic and pharmacologic manipulation of STARS/MKL1/SRF pathway significantly alter insulin action: 1) Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation; 2) reduced STARS expression increased insulin signalling and glucose uptake, and 3) SRF inhibition by CCG-1423 reduced nuclear MKL1, improved glucose uptake, and improved glucose tolerance in insulin resistant mice in vivo. Thus, SRF pathway alterations are a signature of insulin resistance which may also contribute to T2D pathogenesis and be a novel therapeutic target. Skeletal muscle samples were obtained from 10 subjects with type 2 diabetes, 25 subjects with a family history of type 2 diabetes (one or both parents), and 15 subjects with no family history of type 2 diabetes. In this analysis RNA was isolated for cRNA preparation and hybridized to Affymetrix Human Genome U133 Plus 2.0 microarrays.
2011-03-01 | E-GEOD-25462 | biostudies-arrayexpress
Project description:Type 2 Diabetes (T2D) is a complex metabolic disorder due to a progressive insulin secretory defect on the background of insulin resistance. We found a muscle specific lncRNA we named TDNC1(T2D down-regulated non-coding RNA 1) whose expression is reduced in T2D patients as well as young individuals with family history of T2D. We used Microarray to assess for global gene expression pattern following ectopic expression of this lncRNA.
2018-06-06 | GSE70365 | GEO
Project description:Mechanistic insights into the molecular events by which exercise enhances the skeletal muscle phenotype are lacking, particularly in the context of type 2 diabetes. Here we unravel a fundamental role for exercise-responsive cytokines (exerkines) on skeletal muscle development and growth in individuals with normal glucose tolerance or type 2 diabetes. Acute exercise triggered an inflammatory response in skeletal muscle, concomitant with an infiltration of immune cells. These exercise effects were potentiated in type 2 diabetes. In response to contraction or hypoxia, cytokines were mainly produced by endothelial cells and macrophages. The chemokine CXCL12 was induced by hypoxia in endothelial cells, as well as by conditioned medium from contracted myotubes in macrophages. We found that CXCL12 was associated with skeletal muscle remodeling after exercise and differentiation of cultured muscle. Collectively, acute aerobic exercise mounts a non-canonical inflammatory response, with an atypical production of exerkines, which is potentiated in type 2 diabetes.
2022-07-06 | GSE202295 | GEO
Project description:Circadian rhythm disruption is associated with skeletal muscle dysfunction within the blind Mexican Cavefish
2023-01-13 | MSV000091062 | MassIVE
Project description:We determined the expression profiles in skeletal muscle from people with type 2 diabetes, first degree relatives, and healthy control individuals by microarray experiments. All subjects were Caucasian males and biopsies were taken after a controlled metabolic period of a two hour hyperinsulinemic euglycemic clamp. Our results show for the first time that insulin signaling is significantly downregulated in people with type 2 diabetes, whereas it is significantly upregulated in first degree relatives. Furthermore, we identify several new genes in skeletal muscle from first degree relatives that have an altered gene expression compared to healthy controls.
2010-01-28 | E-MEXP-2559 | biostudies-arrayexpress
Project description:Analysis of gene expression associated with exercise response. The hypothesis tested was that individuals with Type 2 Diabetes that failed to demonstrate exercise-induced metabolic improvements would also reflect this lack of response in their skeletal muscle transcriptional profile at baseline. Of 186 genes identified by microarray analysis, 70% were upregulated in Responders and downregulated in Non-responders. Several genes involved in substrate metabolism and mitochondrial biogenesis differed significantly between the groups at baseline. This differential baseline gene expression indicated that Non-responders had blunted oxidative capacity. Total RNA extracted from baseline samples of skeletal muscle of obese individuals with Type 2 Diabetes who were characterized as either Responders or Non-responders was examined for differential expression of exercise response-assocated genes.
2015-11-10 | E-GEOD-74782 | biostudies-arrayexpress
Project description:Insulin-stimulated muscle glucose uptake is a key process to alleviate hyperglycemia. This process depends on the redistribution of glucose transporters to the muscle surface membrane following phosphorylation of TBC1D1 and TBC1D4. Genetic evidence from a TBC1D4 loss-of-function mutation in human skeletal muscle is associated with an increased risk of type 2 diabetes (T2D). However, little is known about the potential regulating interactors of TBC1D4 in skeletal muscle. Here, we sought to identify interactors of TBC1D4 in human skeletal muscle by an unbiased proteomics approach. We detected 76 proteins as candidate TBC1D4 interactors, whereof 12 were regulated by insulin stimulation including known proteins involved in glucose metabolism (e.g. 14-3-3 proteins and ACTN4). TBC1D1 also co-precipitated with TBC1D4 and vice versa in both human and mouse skeletal muscle. This interaction was not regulated by insulin or exercise in young healthy lean individuals. In contrast, we observed an altered interaction as well as compromised insulin-stimulated phospho-regulation of the TBC1D1-TBC1D4 complex in muscle of obese individuals with T2D. In conclusion, we provide a list of TBC1D4 interactors in human and mouse skeletal muscle. These protein interactors serve as potential regulators of TBC1D4 function and thus insulin-stimulated glucose uptake in skeletal muscle.
2022-03-01 | PXD026225 | Pride