Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limitin g enzyme in the hexosamine biosynthetic pathway, which plays an important r ole in hyperglycemia-induced insulin resistance. To evaluate the role of GF AT1 expression, we analyzed the expression profiles of GFAT1 mRNA in variou s human tissues using reverse transcriptase-polymerase chain reaction. We r eport here the identification and cDNA cloning of a novel GFAT1splice varia nt expressed abundantly in skeletal muscle and heart. This subtype, designa ted GFAT1-L, contains a 54-bp insertion within the GFAT1coding sequence. Re combinant GFAT1-L protein possessed functional GFAT activities and biochemi cal characteristics similar to GFAT1. Previously, GFAT1 was considered a si mplex enzyme. The identification of a novel GFAT1 subtype possessing functi onal enzymatic activity and tissue-specific expression should provide addit ional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.