Dataset Information

Insulin attenuates TNF?-induced hemopexin mRNA: An anti-inflammatory action of insulin in rat H4IIE hepatoma cells.

ABSTRACT: Proinflammatory cytokines, including TNF-? and IL-6, can contribute to insulin resistance. Conversely, insulin has some actions that can be considered anti-inflammatory. Hemopexin is a Class 2 acute phase reactant and control of its transcription is predominantly regulated by IL-6, with TNF-? and IL-1? also inducing hemopexin gene expression. Thus, we asked whether insulin could inhibit the ability of TNF-? to stimulate hemopexin mRNA expression. In cultured rat hepatoma (H4IIE) cells, TNF-? significantly increased hemopexin mRNA accumulation. The TNF-?-induced increase of hemopexin mRNA was dramatically attenuated by insulin, even though TNF-? reduced peak insulin activation of ERK. Thus, even though TNF-? can contribute to insulin resistance, the residual insulin response was still able to counteract TNF-? actions.

SUBMITTER: Franklin JL

PROVIDER: S-EPMC5614554 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Insulin attenuates TNFα-induced hemopexin mRNA: An anti-inflammatory action of insulin in rat H4IIE hepatoma cells.

Franklin J Lee JL Bennett William L WL Messina Joseph L JL

Biochemistry and biophysics reports 20170105

Proinflammatory cytokines, including TNF-α and IL-6, can contribute to insulin resistance. Conversely, insulin has some actions that can be considered anti-inflammatory. Hemopexin is a Class 2 acute phase reactant and control of its transcription is predominantly regulated by IL-6, with TNF-α and IL-1β also inducing hemopexin gene expression. Thus, we asked whether insulin could inhibit the ability of TNF-α to stimulate hemopexin mRNA expression. In cultured rat hepatoma (H4IIE) cells, TNF-α sig ...[more]

PMID: 28956007

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Project description:Transcriptional profiling of insulin exposed H4IIE cells at different time points (6h-24h) to 100 nM insulin, with untreated solvent control cells (blanks). The central role of hepatic insulin resistance in pandemic metabolic diseases urges investigation of the underlying mechanisms of its development and pathogenesis. Besides genetic susceptibility and lifestyle factors, environmental pollutants are suggested risk factors. In order to appraise the role of the thousands of pollutants we are daily exposed to, stable, robust and high throughput cell-based systems should be developed. In this context, it is of paramount importance to select an in vitro system which mimics in vivo insulin responses as close as possible. Therefore, this study was designed to evaluate if the rat H4IIE hepatoma cell line is a physiologically relevant model to study hepatic insulin responses. DNA microarray analysis, real-time PCR and flow cytometric cell cycle analysis were used to assess the relevance of the insulin response in H4IIE cells. Insulin dose dependently stimulated H4IIE growth. Time dependency of the insulin response was shown with real-time PCR for the known insulin responsive genes: Fasn, Pck1 and Irs2. Based on these results, microarray analysis was performed on H4IIE cells exposed to insulin (100 nM) for 6h and 24h. Genes related to carbohydrate (glycolysis and gluconeogenesis) and lipid metabolism (glycerolipid metabolism, cholesterol synthesis and fatty acid oxidation) were most profoundly afflicted, in accordance with in vivo insulin action in liver. Since changes in carbohydrate and lipid metabolism are pivotal in the pathogenesis of insulin resistance, the presence of a physiological relevant insulin response in H4IIE cells pleads for further testing of its potential use in research on pollutant-driven insulin resistance. Microarray analysis was performed on H4IIE cells exposed to insulin (100 nM) for 6h and 24h. A separate v+2 A-optimal hybridization design was used for each time-point. Using this design each exposure condition is represented by three biological replicates, with each biological replicate analysed in technical duplicate while applying the dye swap principle to correct for dye bias.

Dataset Information

Insulin attenuates TNF?-induced hemopexin mRNA: An anti-inflammatory action of insulin in rat H4IIE hepatoma cells.

Publications

Insulin attenuates TNFα-induced hemopexin mRNA: An anti-inflammatory action of insulin in rat H4IIE hepatoma cells.

Similar Datasets

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