Functional glucokinase isoforms are expressed in rat brain

Recently, the description of glucokinase mRNA in certain neuroendocrine cel ls has opened new ways to characterize this enzyme in the rat brain. In thi s study we found glucokinase mRNA and a similar RNA splicing pattern of the glucokinase gene product in rat hypothalamus and pancreatic islets; the mR NA that codes for B1 isoform was the most abundant, with minor amounts of t hose coding for the B2, P1, P2, P1/B2, and P2/B2 isoforms. Glucokinase gene expression in rat brain gave rise to a protein of 52 kDa with a high appar ent K-m for glucose and no product inhibition by glucose 6-phosphate, with a contribution to the total glucose phosphorylating activity of between 40 and 14%; the hypothalamus and cerebral cortex were the regions of maximal a ctivity. Low and high K-m hexokinases were characterized by several criteri a. Also, using RT-PCR analysis we found a glucokinase regulatory protein mR NA similar to that previously reported in liver. These findings indicate th at the glucokinase present in rat brain should facilitate the adaptation of this organ to fluctuations in blood glucose concentrations, and the expres sion of glucokinase and GLUT-2 in the same hypothalamic neurons suggests a role in glucose sensing.