Reassessing the Role of Diacylglycerols in Insulin Resistance

Skeletal muscle (SM) insulin resistance (IR) plays an important role in the burden of obesity, particularly because it leads to glucose intolerance and type 2 diabetes. Among the mechanisms thought to link IR to obesity is the accumulation, in muscle cells, of different lipid metabolites. Diacylglycerols (DAGs) are subject of particular attention due to reported interactions with the insulin signaling cascade. Given that SM accounts for the majority of insulin-stimulated glucose uptake, this review integrates recent observational and mechanistic works with the sole focus on questioning the role of DAGs in SM IR. Particular attention is given to the subcellular distributions and specific structures of DAGs, highlighting future research directions towards reaching a consensus on the mechanistic role played by DAGs.