Dataset Information

Genetic variation in insulin-induced kinase signaling.

ABSTRACT: Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.

SUBMITTER: Wang IX

PROVIDER: S-EPMC4547848 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Genetic variation in insulin-induced kinase signaling.

Wang Isabel Xiaorong IX Ramrattan Girish G Cheung Vivian G VG

Molecular systems biology 20150722 7

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction d ...[more]

PMID: 26202599

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Dataset Information

Genetic variation in insulin-induced kinase signaling.

Publications

Genetic variation in insulin-induced kinase signaling.

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