1. Acetylation and insulin resistance: a focus on metabolic and mitogenic cascades of insulin signaling.
- Author
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Emamgholipour, Solaleh, Ebrahimi, Reyhane, Bahiraee, Alireza, Niazpour, Farshad, and Meshkani, Reza
- Subjects
GLUCOSE metabolism ,ACETYLTRANSFERASES ,BIOCHEMISTRY ,CELLULAR signal transduction ,GENE expression ,HISTONES ,HOMEOSTASIS ,INSULIN resistance ,PHENOMENOLOGY ,METABOLIC disorders ,PHOSPHORYLATION ,TYROSINE ,HISTONE deacetylase ,MICRORNA ,GLUCOSE metabolism disorders ,EPIGENOMICS ,DISEASE risk factors - Abstract
Insulin resistance is associated with an increased risk of several metabolic disorders including type 2 diabetes, hypertension and cardiovascular diseases. Advances over the last decade have expanded our understanding of the molecular mechanisms underlying insulin resistance; however, many details of the mechanisms causing insulin resistance remain unknown. Recently, attention has shifted toward the role of epigenetics in insulin resistance. In this regard, acetylation of the histone tails has been widely investigated for its role in influencing both metabolic and mitogenic cascades of insulin signaling. More specifically, histone acetyltransferases and histone deacetylases, as major modulators of chromatin accessibility and gene expression, have been studied to determine a possible interconnectivity between the special effects of lysine acetylation status and tyrosine phosphorylation networks on the target proteins of downstream pathways involved in both metabolic and mitogenic cascades of insulin signaling. There is accumulating evidence for the post-translational modification effects of IGFR, InsR, IRS1/2, PI3K, Akt, GLUT4, FoxO, PGC-1α, PPAR, AMPK and MAPKs on insulin resistance and glucose homeostasis. In this paper, we review the importance of acetylation of these factors in the regulation of insulin signaling and glucose metabolism, with a primary focus on the target proteins of downstream signaling of insulin. We also provide an update on the interplay between epigenetic modification and the cellular genome in the context of insulin signaling and describe the possible effect of the environment on this epigenetic regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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