title: Influence of diabetes surgery on a gut-brain-liver axis regulating food intake and internal glucose production.
abstract: It has long been known that the brain, especially the hypothalamus, can modulate both insulin secretion and hepatic glucose fluxes, via the modulation of the sympathetic system (promoting glycogen breakdown) and the parasympathetic system (stimulating glycogen deposition). Central insulin signalling or hypothalamic long-chain fatty acid oxidation can also control insulin's suppression of endogenous glucose production. Interestingly, intestinal gluconeogenesis can initiate a portal glucose signal, transmitted to the hypothalamus via the gastrointestinal nervous system. This signal may modulate the sensation of hunger and satiety and insulin sensitivity of hepatic glucose fluxes as well. The rapid improvements of glucose control taking place after gastric bypass surgery in obese diabetics has long been mysterious. Actually, the specificity of gastric bypass in obese diabetic mice relates to major changes in the sensations of hunger and to rapid improvement in insulin sensitivity of endogenous glucose production. We have shown that an induction of intestinal gluconeogenesis plays a major role in these phenomena. In addition, the restoration of the secretion of glucagon like peptide 1 and consequently of insulin plays a key additional role to improve postprandial glucose tolerance. Therefore, a synergy between incretin effects and intestinal gluconeogenesis might be a key feature explaining the rapid improvement of glucose control in obese diabetics after bypass surgery.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U855, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D050110:Bariatric Surgery; D001921:Brain / Q000502:physiology*; D003920:Diabetes Mellitus / Q000601:surgery*; D004435:Eating / Q000502:physiology*; D015390:Gastric Bypass; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis*; D006801:Humans; D007422:Intestines / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D009765:Obesity
chemical_list: D005947:Glucose