Genetic variation in insulin‐induced kinase signaling

Molecular Systems Biology

Isabel Xiaorong Wang²  Girish Ramrattan¹ 

[1] Howard Hughes Medical Institute, Chevy Chase, MD, USA;Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA

关键词: DNA variants;    individual variation;    insulin response;    signal transduction;    type 2 diabetes;   

DOI  :  10.15252/msb.20156250

来源: Wiley

【 摘 要 】

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.

Synopsis

Genetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.

• Extensive individual variation is observed in insulin-induced activation of signal transduction.
• The variation in signaling response is propagated downstream to influence gene expression and cell growth.
• There is a genetic component to the individual differences in signaling and gene expression response to insulin.

【 授权许可】

CC BY   
© 2015 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.