The levels of the anorexigenic peptides, POMC and CART, are known to increase in hyperglycemic conditions, whereas the levels of the orexigenic peptides, NPY and AgRP, decrease in the same conditions. Our results confirmed this pattern of neuropeptide expression in glucose-challenged control rats. However, no differences in the expression of AgRP, NPY and CART were observed between the saline-treated and glucose-treated GK knockdown animals. Interestingly, POMC expression actually decreased in glucose-treated GK knockdown animals. These results are congruent to (and may be the cause of) the augmented food intake as well as the decreased satiety observed in the GK knockdown animals in our study. However, GK inhibition in the AN has recently been shown to decrease food intake in rats25. These findings may indicate that the role of GK on food intake is cell type-dependent in a manner similar to that observed for GKRP, which is present in tanycytes, and exerts opposing effects on GK compartmentalization compared to that observed in hepatocytes15.