Human Insulin Resistance and Thiazolidinedione-Mediated Insulin Sensitization
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE13070 | GEO | 2010/05/17
SECONDARY ACCESSION(S): PRJNA109687
REPOSITORIES: GEO
Similar Datasets
Project description:Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPAR? ligands. We transcriptionally profiled 364 biopsies gathered from 72 human subjects harvested before and after hyperinsulinemic-euglycemic clamp, at baseline and after three-month TZD treatment. Subjects range from insulin-sensitive to insulin-resistant. Insulin resistant subjects responded to TZD treatment with varied improvements in insulin sensitivity, thus they were ranked by their degree of TZD response to define responder and non-responder subgroups. Skeletal muscle biopsies were obtained from vastus lateralis before and after hyperinsulinemic-euglycemic clamp, at baseline and after three-month TZD treatment. Adipose tissue biopsies were obtained from abdominal subcutaneous before clamp, at baseline and after three-month TZD treatment. *** CEL files not provided for 40 Samples. ***
2010-05-17 | E-GEOD-13070 | 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:The goal of this study was to analyse the effect of a 12 weeks treatment with rosiglitazone on insulin sensitivity in the muscle of type 2 diabetic patients. Ten diabetic patients were submitted to a 3 hours euglycemic-hyperinsulinemic clamp. Skeletal muscle biopsies were taken before and after the clamp. Samples from the same patients (obtained before and after the clamp) were hybridized on the same microarray. Biopsie taken before the clamp was considered as the control. Then, the patients were treated with rosiglitazone, agonist of PPAR gamma, during 12 weeks. After the treatment, all the patients were submitted to a second 3 hours euglycemic-hyperinsulinemic clamp. Skeletal muscle biopsies for 7 patients were taken before and after the clamp. Samples from the same patients (obtained before and after the clamp) were hybridized on the same microarray. Biopsie taken before the clamp was considered as the control. Set of arrays that are part of repeated experiments Compound Based Treatment: patient biopsies taken before (no) and after (yes) rosiglitazone (TZD) treatment`
2018-04-20 | GSE12844 | GEO
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:OC samples: muscle biopsy samples collected from insulin sensitive / insulin resistant obese indivduals before undergoing a hyperinsulinemic-euglycemic clamp. Subjects were previously categorized for the rate of fatty acid release from adipose tissue into the bloodstream as a measure of insuline resistance. Low-FA, Med-FA, and High-FA stand for low, medium, and high rate of release.
2017-08-02 | ST000841 | MetabolomicsWorkbench
Project description:The goal of this study was to analyse the effect of a 12 weeks treatment with rosiglitazone on insulin sensitivity in the adipose tissue of type 2 diabetic patients. Diabetic patients were submitted to a 3 hours hyperinsulinemic- euglycemic clamp. Adipose tissue biopsies were taken before and after the clamp, labelled A & B respectively. Then, the patients were treated with rosiglitazone, agonist of PPAR gamma, during 12 weeks. After the treatment, all the patients were submitted to a second 3 hours hyperinsulinemic-euglycemic clamp. Adipose tissue biopsies were taken before and after the clamp, labelled C & D respectively.
2018-04-20 | GSE12894 | GEO
Project description:This study was undertaken to test the hypothesis that short term exposure (4 hours) to physiologic hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response, independently of glycemic status. We performed euglycemic hyperinsulinemic (80 mU/m2/min) clamps in 12 healthy, insulin sensitive subjects with no family history of diabetes followed by biopsies of the vastus lateralis muscle taken basally and after 30 and 240 minutes of insulin infusion. Gene expression profiles were generated using Affymetrix HG-U133A arrays. No probe sets had significantly altered expression at 30 minutes of the insulin clamp, but 121 probe sets (117 upregulated and 4 downregulated) were significantly altered after 240 minutes. Hyperinsulinemia in normal, healthy human subjects increased the mRNAs for a number of inflammatory genes and transcription factors. Microarray and quantitative RT-PCR revealed the upregulation of chemokine, cc motif, ligand 2 (CCL2), CCL8, thrombomodulin (THBD), ras-related associated with diabetes (RRAD), metallothionein (MT), and serum/glucocorticoid regulated kinase (SGK), and downregulation of CITED2 (a CREB-binding protein-interacting transactivator), a known coactivator of PPAR-alpha. Interestingly, SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to hyperinsulinemia. A control saline infusion performed on 3 normal, healthy subjects without a family history of diabetes demonstrated that the genes altered following the euglycemic-hyperinsulinemic clamp were due to insulin and independent of biopsy removal. This study demonstrates that insulin acutely regulates the expression of genes involved in inflammation and transcription, and identifies several candidate genes/pathways for further investigation. Keywords: Gene Expression, Skeletal Muscle, Insulin Action, Euglycemic Hyperinsulinemic Clamp, Inflammation
2007-09-20 | GSE9105 | GEO
Project description:This study was undertaken to test the hypothesis that short term exposure (4 hours) to physiologic hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response, independently of glycemic status. We performed euglycemic hyperinsulinemic (80 mU/m2/min) clamps in 12 healthy, insulin sensitive subjects with no family history of diabetes followed by biopsies of the vastus lateralis muscle taken basally and after 30 and 240 minutes of insulin infusion. Gene expression profiles were generated using Affymetrix HG-U133A arrays. No probe sets had significantly altered expression at 30 minutes of the insulin clamp, but 121 probe sets (117 upregulated and 4 downregulated) were significantly altered after 240 minutes. Hyperinsulinemia in normal, healthy human subjects increased the mRNAs for a number of inflammatory genes and transcription factors. Microarray and quantitative RT-PCR revealed the upregulation of chemokine, cc motif, ligand 2 (CCL2), CCL8, thrombomodulin (THBD), ras-related associated with diabetes (RRAD), metallothionein (MT), and serum/glucocorticoid regulated kinase (SGK), and downregulation of CITED2 (a CREB-binding protein-interacting transactivator), a known coactivator of PPAR-alpha. Interestingly, SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to hyperinsulinemia. A control saline infusion performed on 3 normal, healthy subjects without a family history of diabetes demonstrated that the genes altered following the euglycemic-hyperinsulinemic clamp were due to insulin and independent of biopsy removal. This study demonstrates that insulin acutely regulates the expression of genes involved in inflammation and transcription, and identifies several candidate genes/pathways for further investigation. Experiment Overall Design: Twelve subjects received a vastus lateralis muscle biopsy followed by a 180-min euglycemic, hyperinsulinemic (80 mU/m2.min) clamp. Muscle biopsies from each subject were homogenized in RNAStat solution (Tel-Test Inc., Friendswood, TX), using a Polytron homogenizer (Brinkmann Instruments Westbury, NY). Total RNA was purified with RNeasy and DNase I treatment (Qiagen, Chatsworth, CA). RNA was prepared for hybridization to Affymetrix (Santa Clara, CA) HG-U133A arrays according to the manufacturerâs instructions.
2008-06-16 | E-GEOD-9105 | biostudies-arrayexpress
Project description:Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Using regression correlation
2005-12-20 | E-GEOD-3881 | biostudies-arrayexpress
Project description:Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
2005-12-21 | GSE3881 | GEO