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.
Thuresson
Eva Rupp
ER
Biovitrum AB, Department of Biology, Strandbergsgatan 49, S-1 1276 Stockholm, Sweden. Eva.Rupp-Thuresson@biovitrum.com
D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D005992:Glycerol-3-Phosphate O-Acyltransferase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases