MicroRNA signature in skeletal muscle in type 2 Diabetes and insulin resistant rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus Homo sapiens
PROVIDER: GSE68226 | GEO | 2015/04/25
SECONDARY ACCESSION(S): PRJNA282052
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-25 | E-GEOD-68226 | biostudies-arrayexpress
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams.
2015-04-25 | GSE68225 | GEO
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams. Skeletal muscle (soleus) was collected from the hind limb of 1 year old male offspring (6 from control dams, 6 from high fat-fed dams) . Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
2015-04-25 | E-GEOD-68225 | biostudies-arrayexpress
Project description:MicroRNA signature in skeletal muscle in type 2 Diabetes and insulin resistant rats
| PRJNA282052 | ENA
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of unmedicated newly diagnosed human pre-diabetics and type 2 diabetics.
2015-04-25 | GSE68224 | GEO
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of unmedicated newly diagnosed human pre-diabetics and type 2 diabetics. Skeletal muscle biopsies were obtained from the vastus lateralis from males with pre-diabetes (PD, n=5) or type 2 diabetes mellitus (T2DM, n=6) along with age and sex-matched healthy volunteers (H, n=5). Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
2015-04-25 | E-GEOD-68224 | biostudies-arrayexpress
Project description:We examined the effects of metformin, a commonly used antidiabetic drug, on gene expression in multiple arteries. Specifically, transcriptional profiles of feed arteries and second branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles as well as aortic endothelial scrapes were examined from obese insulin-resistant Otsuka Long-Evans Tokushima Fatty rats treated with ( n?=?9) or without ( n?=?10) metformin from 20 to 32 weeks of age. Metformin-treated rats exhibited a reduction in body weight, adiposity, and HbA1c ( P?<?0.05). The greatest number of differentially expressed genes (FDR?<?15%) between those treated with and without metformin was found in the red gastrocnemius 2a arterioles (93 genes), followed by the diaphragm 2a arterioles (62 genes), and soleus 2a arterioles (15 genes). We also found that two genes were differentially expressed in aortic endothelial cells (LETMD1 and HMGCS2, both downregulated), one gene in the gastrocnemius feed artery (BLNK, downregulated), and no genes in the soleus and diaphragm feed arteries and white gastrocnemius 2a arterioles. No single gene was altered by metformin across all vessels examined. This study provides evidence that metformin treatment produces distinct gene expression effects throughout the arterial tree in a rat model of obesity and insulin resistance. Genes whose expression was modulated with metformin do not appear to have a clear connection with its known mechanisms of action. These findings support the notion that vascular gene regulation in response to oral pharmacological therapy, such as metformin, is vessel specific. Impact statement This study provides evidence that metformin treatment produces artery-specific gene expression effects. The genes whose expression was modulated with metformin do not appear to have a clear connection with its known mechanisms of action.
| S-EPMC5685263 | biostudies-literature
Project description:The objective of this study was to determine the role of maximum mitochondrial capacity on the variation in insulin sensitivity within a population of patients with type 2 diabetes mellitus (T2DM).Fifty-eight participants enrolled in a cross-sectional design: eight active controls [maximum aerobic capacity (VO(2max)) > 40 ml/kg · min], 17 healthy sedentary controls without a family history (FH-) and seven with a family history (FH+) of diabetes, four obese participants, and 21 patients with T2DM. Mitochondrial capacity was measured noninvasively using (31)P magnetic resonance spectroscopy of the vastus lateralis. Maximal ATP synthetic rate (ATP(max)) was determined from the rate of phosphocreatine (PCr) recovery after short-term isometric exercise.ATP(max) was lower (P < 0.001) in T2DM and higher (P < 0.001) in active as compared with healthy sedentary FH- (active, 1.01 ± 0.2; FH-, 0.7 ± 0.2; FH+, 0.6 ± 0.1; obese, 0.6 ± 0.1; T2DM, 0.5 ± 0.2 mm ATP/sec; ANOVA P < 0.0001). Insulin sensitivity, measured by euglycemic-hyperinsulinemic (80 mIU/m(2) · min) clamp was also reduced in T2DM (P < 0.001) (active, 12.0 ± 3.2; FH-, 7.8 ± 2.2; FH+, 6.8 ± 3.5; obese, 3.1 ± 1.0; T2DM, 3.4 ± 1.6; mg/kg estimated metabolic body size · min; ANOVA P < 0.0001). Unexpectedly, there was a broad range of ATP(max) within the T2DM population where 52% of subjects with T2DM had ATP(max) values that were within the range observed in healthy sedentary controls. In addition, 24% of the T2DM subjects overlapped with the active control group (range, 0.65-1.27 mm ATP/sec). In contrast to the positive correlation between ATP(max) and M-value in the whole population (r(2) = 0.35; P < 0.0001), there was no correlation between ATP(max) and M-value in the patients with T2DM (r(2) = 0.004; P = 0.79).Mitochondrial capacity is not associated with insulin action in T2DM.
| S-EPMC3070252 | biostudies-literature
Project description:Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of the >100 variants associated with T2D and related traits in genome-wide association studies (GWAS), >90% occur in non-coding regions, suggesting a strong regulatory component to T2D risk. Here to understand how T2D status, metabolic traits and genetic variation influence gene expression, we analyse skeletal muscle biopsies from 271 well-phenotyped Finnish participants with glucose tolerance ranging from normal to newly diagnosed T2D. We perform high-depth strand-specific mRNA-sequencing and dense genotyping. Computational integration of these data with epigenome data, including ATAC-seq on skeletal muscle, and transcriptome data across diverse tissues reveals that the tissue-specific genetic regulatory architecture of skeletal muscle is highly enriched in muscle stretch/super enhancers, including some that overlap T2D GWAS variants. In one such example, T2D risk alleles residing in a muscle stretch/super enhancer are linked to increased expression and alternative splicing of muscle-specific isoforms of ANK1.
| S-EPMC4931250 | biostudies-literature
Project description:The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.
| S-EPMC4873835 | biostudies-other