Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action?

Abstract

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

Keywords: SIRT1/HDAC; acetyltransferase; deacetylase; insulin signaling; p300/CBP.

Fig. 1.

Theoretical overview of acetylation in insulin signaling and glucose metabolism. (A) KATs and DACs have been shown to regulate the acetylation patterns of various proteins within the insulin signaling pathway. However, the exact pattern of acetylation and the effect acetylation plays in response to insulin stimulation is not known. (B) Acetylation within glucose metabolism has been shown to regulate glycolytic enzymes and promote glycogen synthesis. However, the dynamics of acetylation patterns within these pathways, and the KATs and DACs that regulate them, following insulin stimulation, are not known. (C) Insulin stimulation may activate ACLY within the cytosol that produces acetyl CoA, from Citrate, required for subsequent acetylation of target proteins.