Relationship between insulin sensitivity and gene expression in human skeletal muscle (Study B)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE161720 | GEO | 2020/11/19
REPOSITORIES: GEO
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Project description:To identify genes correlated to insulin sensitivity in skeletal muscle, we studied 38 non-diabetic men from Malmö, Sweden. Briefly, the Malmö Exercise Intervention cohort consists of sedentary but otherwise healthy male subjects from southern Sweden. They all have European ancestry and 18 of them have a first-degree family member with T2D. The mean age and body mass index (BMI) were 37.71 ± 0.71 years and 28.47 ± 0.48 kg/m2, respectively, and the mean 1/the homeostatic model assessment-insulin resistance (HOMA-IR) was 0.69 ± 0.04
2020-11-19 | GSE161719 | GEO
Project description:The aim of this study is to define the molecular alterations occurring in human adipose tissue leading to its dysfunction. While obesity (defined by BMI>30) is strongly associated with insulin resistance and metabolic disorders, some individuals with obesity remain insulin sensitive. Therefore, in this study, we have considered a control group (lean, insuln sensitive: BMI<25, HOMA-IR<2), a group with overweight/obesity but without insulin resistance (BMI>25, HOMA-IR<2) and a group with overweight and insulin resistance (BMI>25, HOMA-IR>3) to dissect the transcriptional changes in viscreal adipose tissue due to increased fat mass, and those associated with metabolic disorder.
2021-02-28 | GSE165932 | GEO
Project description:Context: An increase in maternal insulin resistance (IR) during pregnancy is essential for normal fetal growth. The mechanisms underlying this metabolic adaptation to pregnancy are poorly understood. Placenta factors are believed to instigate and maintain these metabolic changes, as IR decreases shortly after delivery. Methylation of placental gene loci that are common targets for miRNAs, are associated with maternal IR. Objective: We hypothesized that placental miRNAs targeting methylated loci are associated with maternal IR during late pregnancy. Methods: Placental miRNA expression was measured via small RNA-sequencing in a subset of 40 placentas selected by maternal pre-gravid BMI and neonatal adiposity. Results: Median maternal age was 27.5 years, with a median pre-pregnancy BMI of 24.7 kg/m2, and median HOMA-IR of 2.9. Among the five selected miRNA, near delivery maternal HOMA-IR correlated with the placental expression of miRNA-371b-3p (r=0.25; p=0.008) and miRNA-3940-3p (r=0.32; p=0.0004) across the 132 individuals. After adjustment for confounding variables, placental miRNA-3940-3p expression remained significantly associated with HOMA-IR (β=0.16; p=0.03). Conclusion: Placental miRNA may have an autocrine or paracrine effect - regulating placental genes which play a role in modulating maternal IR.
2023-03-01 | GSE169523 | GEO
Project description:The aim of this study was therefore to investigate molecular mechanisms associated with insulin sensitivity in skeletal muscle by relating global skeletal muscle gene expression with a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). To identify genes with skeletal muscle expression related to insulin sensitivity, we obtained muscle biopsies from 38 non-diabetic participants in study A. We then profiled muscle gene expression using Affymetrix oligonucleotide microarrays (Affymetrix Custom Array NuGO-Hs1a520180 GeneChip). To replicate the findings from study A, we included 9 non-diabetic participants from study B. We performed skeletal muscle gene expression profiling from these participants using the Agilent oligonucleotide microarrays (Agilent-G4112F (Feature Number version)). Insulin sensitivity was estimated using the 1/HOMA-IR method calculated from the oral glucose tolerance test (OGTT) values. This SuperSeries is composed of the SubSeries listed below.
2020-11-19 | GSE161721 | GEO
Project description:Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance. Paired human subcutaneous (sc) and omental (om) adipose tissue samples obtained from 4 non-diabetic adipose tissue donors (4 M; BMI: 20.8-27.5 Kg/m2) were incubated without (Ctr) or with dexamethasone (Dex, 3 M-NM-<M) for 24 h.
2014-08-18 | E-GEOD-42902 | biostudies-arrayexpress
Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between insulin resistance high risk subjects and insulin resistance low risk subjects Participants enrolled in this study were recruited in the overnight fasted state, then the collection and processing of glucose (fasting, 30, 60 and 120 minutes) and insulin from blood samples, hemoglobin A1c (HbA1c) , assessment of medical history, socio-demographic characteristics, lifestyle factors, blood pressure and anthropometric and body composition measurements were conducted. During baseline visit, participants were asked to refrain from eating, drinking and oral hygiene procedures for at least 1-hour prior to saliva collection.5 ml of unstimulated whole saliva samples were consistently collected, stabilized and preserved, the sample supernatants were reserved at -80°C prior to assay. Based on the homeostasis model assessment of insulin resistance (HOMA-IR), using the formula [HOMA-IR= (fasting glucose*fasting insulin)/405], participants were divided into 2 groups: IR high risk group (HOMA-IR value ?2.5) and IR low risk group (HOMA-IR value <2.5). Total RNA was extracted from saliva and subjected to gene expression microarray analysis using Affymetrix human genome 2.0 plus array
2015-04-10 | E-GEOD-67738 | biostudies-arrayexpress
Project description:There is increasing evidence that metabolic diseases originate in early life, and epigenetic changes have been implicated as key drivers of this early life programming. This led to the hypothesis that epigenetic marks present at birth may predict an individual’s future risk of obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks in blood of newborn children were associated with BMI and insulin sensitivity later in childhood. DNA methylation was measured in neonatal blood spot samples of 439 children using the Illumina Infinium 450k BeadChip. Associations were assessed between DNA methylation at birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and HOMA-IR at age 5 years, as well as birthweight, maternal BMI and smoking status. No individual methylation sites at birth were associated with obesity or insulin sensitivity measures at 5 years. DNA methylation in 69 genomic regions at birth was associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The methylation changes were generally small (<5%), except for a region near the non-coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at birth and BMI in childhood was observed (P=0.001). Associations were also found between DNA methylation, maternal smoking, and birth weight. We identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. These findings support the mounting evidence on the role of epigenetics in programming of metabolic health. Whether many of these small changes in DNA methylation are causally related to the health outcomes, and of clinical relevance, remains to be determined, but the nc886 region represents a promising obesity risk marker that warrants further investigation.
2017-09-09 | GSE103657 | GEO
Project description:Subcutaneous adipose tissue (SAT) is classically viewed as a metabolic buffer for lipid deposition during positive caloric balance, while visceral adipose tissue (VAT) is viewed as the dominant contributor and prime mediator of insulin resistance (IR) and cardiometabolic disease risk. Nevertheless, a growing body of data suggests that similar morphologic and molecular changes may occur in SAT as in VAT during obesity. In addition, while pro-inflammatory immune changes within adipose are thought to drive IR there is increasing data implicating a role for adipocytes and stromal populations especially in humans. Here, we identified a transcriptional landscape of IR in SAT of 220 humans across the spectrum of obesity and IR states, highlighting a broad range of metabolic pathways central to IR. Using single cell and nucleus deconvolution and statistical learning techniques, we identified a 35-gene signature that (1) achieved high predictive accuracy for homeostatic model of IR (HOMA-IR) across BMI; (2) was expressed across a variety of non-immune cell populations (most prominently adipocytes and adipocyte stem and precursor cells [ASPCs]), with primarily “protective” IR associations for adipocyte transcripts and “deleterious” associations for macrophage transcripts; (3) displayed a high concordance between SAT and VAT (greater than non-IR associated genes). Multiple SAT genes exhibited dynamic expression 5-years after weight loss surgery and with insulin stimulation. Finally, using available expression quantitative trait loci in SAT and/or VAT, we demonstrate similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI, suggesting underlying similarities in genetic determinants of IR between adipose depots. These results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and that is shared with VAT, nuancing the current VAT-centric concept of IR in humans.
2024-10-19 | GSE245948 | GEO
Project description:Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.
2014-08-18 | GSE42902 | GEO
Project description:Context: While ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to development of ageing-associated diseases, in human primary muscle stem cells (myoblasts) from community dwelling older individuals we investigated whether differential DNA methylation was associated with IR. Methods: We measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 male/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated Cytosine phosphate Guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR (derived from fasting insulin/glucose) and HbA1c. Results: 38 dmCpGs (false discovery rate (FDR)<0.05), and 8 DMRs (Stouffer<0.05) were associated with HOMA2-IR; 6 dmCpGs and 3 DMRs were robust to adjustment for BMI, including DMRs within T-box transcription factor (TBX1) and nuclear receptor subfamily-2 group F member-2 (NR2F2). HOMA2-IR associated dmCpGs were enriched in genes linked with skeletal muscle development and insulin signalling. 49 dmCpGs were associated with HbA1c, with 48 robust to adjustment for BMI. The only dmCpG associated with both HOMA2-IR and HbA1c was cg13451048, located within Exoribonuclease Family Member 3 (ERI3). HOMA2-IR and HbA1c dmCpGs were not associated with accelerated epigenetic ageing. Conclusions: These findings suggest differential DNA methylation in muscle stem cells may contribute to age-related decline in glycaemic control. The identification of dmCpGs, associated genes and pathways may provide novel targets for pharmacological intervention.
2023-11-16 | GSE221540 | GEO