Intestinal gluconeogenesis: key signal of central control of energy and glucose homeostasis

PURPOSE OF REVIEW: It has been established that the gut is much more than a digestive tract. It has the capacity to participate in the control of energy homeostasis via the secretion of various hormones. It can also contribute to the control of glucose homeostasis via its high glycolytic capacity and a recently described function, gluconeogenesis. RECENT FINDINGS: In addition to its quantitative role in endogenous glucose production, qualitative roles (i.e. central signaling) were recently described for intestinal gluconeogenesis. In relation to the control of energy homeostasis, intestinal gluconeogenesis, via its detection by a hepatoportal glucose sensor, is able to generate a central signal of control of food intake, resulting in enhanced satiety. This mechanism has been suggested to account for 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 especially account for the rapid amelioration of the parameters of insulin resistance occurring after gastric bypass, a specific type of surgery of obesity. SUMMARY: These new findings on the role of intestinal gluconeogenesis in the central control of energy and glucose homeostasis should be of interest for nutritionists and diabetologists. They pave the way to envision new strategies of prevention or treatment of obesity and type 2 diabetes in humans.