Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the first and rate-limiting enzyme for the entry of glucose into the hexosamine biosynthesis pathway (HBP) in mammals. GFAT1, a member of the N-terminal nucleophile class of amidotransferases, converts fructose-6-phosphate into N-acetylglucosamine-6-phosphate. Hyperglycemia-induced insulin resistance, a condition in which exposure to high concentrations of glucose and insulin results in insulin resistance, may result from increased glucose metabolism through the HBP. Hypergylcemia-induced insulin resistance is a characteristic feature of type 2 diabetes. Consequently, GFAT1 is a potential therapeutic target in the treatment of type 2 diabetes.