Expression data from insulin-treated human primary fibroblasts and effects of U0126 on insulin-induced gene expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE21891 | GEO | 2015/08/03
SECONDARY ACCESSION(S): PRJNA126905
REPOSITORIES: GEO
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Project description:We carried out a high throughput analysis of insulin-induced kinase signaling pathways in primary fibroblasts from 35 unrelated individuals. We found that extensive individual variation exists in induction of various signaling pathways. ERK signaling displayed the greatest variation, which led to extensive variation in expression of downstream target genes. Our results suggest that phenotypic variation in kinase signaling mediates variation in downstream processes of insulin response. Future study of such phenotypic variation is important to linking genetic variants to individual susceptibility to complex diseases such as diabetes. Passage-matched primary fibroblasts from 35 unrelated newborns (foreskin) were treated with 100 nM insulin. We measured gene expression levels in each of 35 individuals at baseline, and 1 hour and 6 hours after insulin treatment using expression arrays. In order to examine effects of ERK inhibition on insulin-induced gene expression, we treated fibroblasts from 4 individuals with DMSO or 10uM of U0126 for 1 hour, followed by insulin treatment for one hour and 6 hours. We then harvested cells and measured gene expression in each sample using expression arrays.
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Project description:This model is from the article:
Temporal Coding of Insulin Action through Multiplexing of the AKT Pathway.
Kubota H, Noguchi R, Toyoshima Y, Ozaki Y, Uda S, Watanabe K, Ogawa W, Kuroda S. Mol Cell.
2012 Jun 29;46(6):820-32. 22633957
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Abstract:
One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient and sustained AKT phosphorylation, respectively. The downstream molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase (G6Pase), and glycogen synthase kinase-3β (GSK3β) selectively decoded transient, sustained, and both transient and sustained AKT phosphorylation, respectively. Selective downstream decoding is mediated by the molecules' network structures and kinetics. Our results demonstrate that the AKT pathway can multiplex distinct patterns of blood insulin, such as pulse-like additional and sustained-like basal secretions, and the downstream molecules selectively decode secretion patterns of insulin.
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