Intestinal gluconeogenesis: metabolic benefits make sense in the light of evolution

The intestine, like the liver and kidney, in various vertebrates and humans is able to carry out gluconeogenesis and release glucose into the blood. In the fed post-absorptive state, intestinal glucose is sensed by the gastrointestinal nervous system. The latter initiates a signal to the brain regions controlling energy homeostasis and stress-related behaviour. Intestinal gluconeogenesis (IGN) is activated by several complementary mechanisms, in particular nutritional situations (for example, when food is enriched in protein or fermentable fibre and after gastric bypass surgery in obesity). In these situations, IGN has several metabolic and behavioural benefits. As IGN is activated by nutrients capable of fuelling systemic gluconeogenesis, IGN could be a signal to the brain that food previously ingested is suitable for maintaining plasma glucose for a while. This process might account for the benefits observed. Finally, in this Perspective, we discuss how the benefits of IGN in fasting and fed states could explain why IGN emerged and was maintained in vertebrates by natural selection.

Automated summary

The intestine, like the liver and kidney, can carry out gluconeogenesis and release glucose into the blood. Intestinal glucose is sensed by the gastrointestinal nervous system, which signals the brain regions controlling energy homeostasis and stress-related behavior. Intestinal gluconeogenesis (IGN) is activated by various mechanisms, particularly in nutritional situations and after gastric bypass surgery in obesity. IGN has metabolic and behavioral benefits, possibly signaling the suitability of previously ingested food for maintaining plasma glucose. These benefits may explain why IGN emerged and was maintained by natural selection in vertebrates.