Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling in diabetic skeletal muscle

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Jane Palsgaard

PROVIDER: E-MEXP-2559 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways.

Palsgaard Jane J Brøns Charlotte C Friedrichsen Martin M Dominguez Helena H Jensen Maja M Storgaard Heidi H Spohr Camilla C Torp-Pedersen Christian C Borup Rehannah R De Meyts Pierre P Vaag Allan A

PloS one 20090811 8

<h4>Background</h4>Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing type 2 diabetes, they provide a good model in the search for primary causes of the disease.<h4>Methods/principal findings</h4>We determined gene expression profiles in skeletal muscle biopsies f ...[more]

PMID: 19668377

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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.

Dataset Information

Gene expression profiling in diabetic skeletal muscle

Publications

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways.

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