A novel function of intestinal gluconeogenesis: Central signaling in glucose and energy homeostasis

The gut can contribute to the control of glucose homeostasis by its high glycolytic capacity and a recently described function, gluconeogenesis. In addition to its quantitative role in endogenous glucose production, a qualitative role of central signaling was recently described for intestinal gluconeogenesis. Relating to the control of energy homeostasis, intestinal gluconeogenesis, by its detection by a hepatoportal glucose sensor, is able to generate a central signal promoting a decrease in food intake. This mechanism may contribute to the well-known satiety effect initiated by food protein. In relation to the control of glucose homeostasis, intestinal gluconeogenesis has been suggested to be a key factor of the central enhancement of insulin sensitivity for the whole body. It may account for the rapid amelioration of insulin resistance occurring after gastric bypass, a specific type of surgery for morbid obesity. Because these beneficial effects may take place in the context of established physiopathology, they allow one to envision new strategies of prevention or treatment of obesity and type 2 diabetes in humans.