Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from primary hepatocytes isolated from miR-143DOX mice

ABSTRACT: The contribution of altered posttranscriptional gene silencing (PTGS) to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. We have described that expression of microRNAs (miR)-143 and -145 is dysregulated in genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, causes insulin resistance and impaired insulin-stimulated AKT activation. We used microarrays to analyze the underlying molecular mechanisms of miR-143-mediated development of insulin resistance. miR-143DOX mice (n=3) and wildtype littermate controls (n=3) were treated with doxycycline via the drinking water to induce miR-143 overexpression in the transgenic animals. Primary hepatocytes were isolated for RNA extraction and hybridization on Affymetrix microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Jens Bruening

PROVIDER: E-GEOD-26460 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism.

Jordan Sabine D SD Krüger Markus M Willmes Diana M DM Redemann Nora N Wunderlich F Thomas FT Brönneke Hella S HS Merkwirth Carsten C Kashkar Hamid H Olkkonen Vesa M VM Böttger Thomas T Braun Thomas T Seibler Jost J Brüning Jens C JC

Nature cell biology 20110327 4

The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected ...[more]

PMID: 21441927

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Project description:Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus (T2D) and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism 1,2,3. MicroRNA (miR)-dependent posttranscriptional gene silencing has recently been recognized to control gene expression in disease development and progression including that of insulin-resistant T2D. MiRs, whose deregulation alters hepatic insulin sensitivity include miR-143, miR-181 and miR-103/107. Here we report that expression of miR-802 is increased in liver of two obese mouse models and of obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, while reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Tcf2 as a target of miR-802-dependent silencing and shRNA-mediated reduction of Tcf2 in liver causes glucose intolerance, impairs insulin signaling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Tcf2 improves insulin sensitivity in db/db mice. Thus, the present study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism via targeting Tcf2 and assigns Tcf2 an unexpected role in the control of hepatic insulin sensitivity. Adenoviruses (Ad5) encoding either GFP (Ad-Ctrl 1-3) or shTcf2 (Ad-shTcf2 1-4) were injected into the tail vein of C57BL/6 mice at 1x10E10 viral particles (VP) per gram bodyweight. Biotin-labeled cDNA was synthesized using GeneChip Whole Transcript Sense Labeling Assay (Affymetrix) according to vendorM-bM-^@M-^Ys instructions. After fragmentation, cDNAs were hybridized for 17h at 45M-BM-0C on Affymetrix Mouse Gene 1.0 ST Arrays. The Arrays were washed and stained in the GeneChip Fluidics Station 450 and scanned on a GeneChip Scanner 3000 7G (Affymetrix). Data intensities were log transformed and normalized with a quantile normalization method using Affymetrix Power Tools. Differentially expressed genes were identified according to statistical evidence indicated by Student's t-test and fold change statistics

Dataset Information

Expression data from primary hepatocytes isolated from miR-143DOX mice

Publications

Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism.

Similar Datasets

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