[Glucose sensing: from gut to brain]

The interactions between glucose and energy homeostasis are well known. In particular, a high portal vein glucose concentration suppresses food intake. Numerous studies point to a glucose-sensing mechanism involving nerves present in the wall of the portal vein. We have studied the expression of genes involved in gluconeogenesis in the rat and human intestine, in terms of mRNA and protein levels and enzyme activity. Intestinal glucose production was quantified by using a combination of (3-3H) glucose tracer dilution and arterio-venous glucose balance. The effect of the portal glucose level on food intake was studied in conscious rats with indwelling portal vein catheters. The hypothalamic consequences of glucose infusion were studied by c-Fos protein immunodetection. All regulatory genes involved in gluconeogenesis were strongly induced by fasting and by a protein-rich diet. In both cases the glucose level in the portal vein increased, an effect that lasted some time after a protein-rich meal. Glucose infusion into the portal vein led to a decrease in food intake and activated hypothalamic regions involved in controlling food intake, in the same way as the protein-rich diet. The effects of portal glucose infusion and of the protein-rich diet were suppressed by inactivating the portal nervous system. These results provide a mechanistic explanation for the effect of satiety induced by a high-protein diet.