Glutamine: Fructose-6-phosphate amidotransferase activity and gene expression are regulated in a tissue-specific fashion in pregnant rats

We examined whether regulation of glutamine: fructose-6-phosphate amidotran sferase (GFA), the rate-limiting enzyme of the hexosamine pathway, is tissu e specific and if so whether such regulation occurs at the level of gene ex pression. We compared GFA activity and expression and levels of UDP-hexosam ines and UDP-hexoses between insulin-sensitive (liver and muscle) tissues a nd a glucose-sensitive (placenta) tissue from 19 day pregnant streptozotoci n diabetic and non-diabetic rats. In pregnant nondiabetic rats GFA activiti es averaged (1521+/-75 pmol/mg protein.min) in the placenta, 895+/-74 in th e liver and 81+/-11 in muscle (p<0.001 between each tissue). In the diabeti c rats, GFA activities were similar to 50 % decreased both in the liver (34 0+/-2 pmol/mg protein min, p<0.05 vs control rats) and in skeletal muscle ( 46+/-3, p<0.05) compared to control rats. In the placenta, GFA activities w ere identical between diabetic (1519+/-112 pmol/mg protein.min) and non-dia betic (1521+/-75) animals. In the liver, the reduction in GFA activity coul d be attributed to a significant decrease in GFA mRNA concentrations, while GFA mRNA concentrations were similar in the placenta between diabetic and non-diabetic animals. UDP-N-acetylglucosamine (UDP-GlcNAc), the end product of the hexosamine pathway, was significantly reduced in the liver and in s keletal muscle but similar in the placenta between diabetic and non-diabeti c rats. In summary, GFA activity and expression and the concentration of UD P-GlcNAc are decreased in the liver but unaltered in the placenta, although GFA activity is almost 2-fold higher in this tissue than in the liver. The se data provide the first evidence for tissue specific regulation of GFA an d for its regulation at the level of gene expression.