[Molecular aspects of a hypothalamic glucose sensor system and their implications in the control of food intake]

Glucose is used mainly as an energy substrate but also as a signalling molecule implied in processes of primary functional concern, such as glucose sensing. Glucose transporter isoform GLUT-2 and especially glucokinase (GK) have been considered as components of a glucose sensor system controlling several key processes such as, glucose-dependent insulin secretion, and stimulation of glucose uptake by liver and skeletal muscle. In the same way this system might modulate feeding behavior and the release of counteregulatory hormones that defend against hypoglycemia. Our findings indicate that GLUT-2 and GK mRNAs and proteins are coexpressed mainly in the hypothalamus of human and experimental animals, in areas implied in the control of food intake. Also, a high Km glucose phosphorylating activity with kinetic properties similar to that reported previously in liver was observed, with a high apparent Km for glucose that displays no product inhibition by glucose-6-phosphate. GK activity may also be regulated by the presence of glucokinase regulatory protein (GKRP), which we have found in the brain of human and experimental animals, in the same areas than GK. Coexpression of GLUT-2, GK and GKRP in areas implied in feeding behavior might play a role in glucose sensing, in which GLUT-2 has a permissive role and the interactions of GK with GKRP made possible a real sensor activity. Furthermore the effects of anorexigenic peptides through its receptors in this system, should facilitate the transduction of signals required to produce a state of satiety.