GLUCOKINASE GENE EXPRESSION IN HYPOTHALAMIC NEURONS E.M. McLain, L.S. Tompkins, V.L. Sutherland, and R.M. Lynch

Pancreatic beta (b) cells secrete insulin in response to increases in glucose metabolism. Glucokinase (GK) catalyzes the rate limiting step in glycolysis setting the sensitivity of b-cells to glucose. Neurons within the homeostatic feeding centers of the hypothalamus (HT) also may sense changes in brain glucose. We detected GK mRNA in adult rat Arcuate (ARC) and Paraventricular nuclei (PVN), Lateral Hypothalamic Area (LHA), Paraventricular nuclei (PVN), and Ventromedial Hypothalamus (VMH) by RT-PCR. Immunochemistry also showed GK protein in some neurons isolated from the HT. The relative expression of GK in adult ARC, LHA and VMN was determined by semiquantitative RT-PCR. Highest levels of expression were observed in the ARC, a hypothalamic region known to integrate sensory input with feeding behavior. Sequencing of the RT-PCR product from ARC indicated 100% identity with islet GK. GK expression also was examined during development and observed from embryonic day 20 through postnatal day 21 in an anatomical pattern similar to adults. The expression of GK in embryonic and adult brain areas involved in energy homeostasis supports the hypothesis of a hypothalamic glucosensing mechanism similar to that of the pancreatic b-cell.