Inhibition of glycerol-3-phosphate acyltransferase as a potential treatment for insulin resistance and type 2 diabetes.

This review focuses on the potential of glycerol-3-phosphate acyltransferase (GPAT) inhibition as a strategy to treat insulin resistance, one of the characteristics of obesity and type 2 diabetes. Inhibition of GPAT, which catalyzes the first and committed step in triacylglyceride synthesis, has the potential to reduce accumulation of ectopic fat in insulin-sensitive organs such as the liver and skeletal muscle. Such an accumulation of fat has been shown to be correlated with insulin resistance. Thus, its reduction by pharmacological treatment is an attractive strategy to treat type 2 diabetes. Potential methods to identify inhibitors for acyltransferases suitable for treatment of human diseases are described.