Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human mesenchymal stem cell derived stromal and adipocyte cells treated with insulin.

ABSTRACT: There are an estimated 21million diabetics in the United States and 150 million diabetics worldwide. The World Health Organization anticipates that these numbers will double in the next 20 years. Metabolic syndrome is a well recognized set of symptoms that increases a patient’s risk of developing diabetes. Insulin resistance is a factor in both metabolic syndrome and Type 2 diabetes. It is characterized by decreased insulin stimulated glucose uptake in peripheral tissues, decreased adiponectin levels, increased adipocyte FFA and cytokine production, and increased insulin and hepatic glucose output. Prevention or reversal of insulin resistance should serve as an important strategy in addressing the growing health concerns posed by the Diabetes epidemic. While increased adiposity is associated with insulin resistance, the role of the cell types present within adipose (adipocytes, pre-adipocytes, endothelial cells, macrophages, fibroblasts, leukocytes and smooth muscle cells) in insulin resistance is unclear. In an effort to begin dissection of this question, we examined the transcriptional response of the buoyant and non-buoyant fractions isolated from insulin sensitive or TNF induced insulin resistant hMSC derived adipocytes before and after treatment with insulin. hMSC derived adipocytes were treated with 0 or 10ng/ml TNF for 24 hours to induce insulin resistance and subsequently serum starved for 5 h followed by treatment with 0 or 20nM insulin for 2 hours. At the end of the incubation period, cells were harvested as is (mixed) or subjected to fractionation to separate the adipocytes (buoyant fraction) and the stromal cells (non-buoyant fraction). These isolated cells were resuspended in RLT buffer to prepare lysates for total RNA isolation using the Qiagen RNeasy kit. Total RNA was submitted to GeneLogic for cRNA preparation using the Affymetrix GenChip IVT kit and hybridization to Affymetrix U133 Plus 2.0 arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Shelley des Etages

PROVIDER: E-GEOD-24422 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.

Lo Kinyui Alice KA Bauchmann Mary K MK Baumann Amy P AP Donahue Christopher J CJ Thiede Mark A MA Hayes Lisa S LS des Etages Shelley Ann G SA Fraenkel Ernest E

PloS one 20110602 6

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lac ...[more]

PMID: 21655096

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Project description:Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesise that its aetiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made M-bM-^@M-^\insulin resistantM-bM-^@M-^] by treatment with tumour necrosis factor (TNF-alpha and then reversed with aspirin and troglitazone (M-bM-^@M-^\re-sensitizedM-bM-^@M-^]). The GES consisted of 5 genes whose expression levels best discriminated between the insulin resistant and insulin re-sensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed using aspirin and troglitazone. This screen identified both known and new insulin sensitising compounds including non-steroidal anti-inflammatory agents, beta-adrenergic antagonists, beta-lactams and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels, P < 0.001). These findings show that GES technology can be used for both discovery of insulin sensitising compounds and characterisation of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalised medicine approach to type 2 diabetes. Three-condition experiment, Vehicle, TNF and TNF+ASA+TGZ with biological replicates: 22 Vehicle, 21 TNF and 21 TNF+ASA+TGZ , independently grown and harvested. One replicate per array.

Dataset Information

Transcription profiling of human mesenchymal stem cell derived stromal and adipocyte cells treated with insulin.

Publications

Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.

Similar Datasets

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