Portal sensing of intestinal gluconeogenesis is a mechanistic link in the diminution of food intake induced by diet protein

Cell Metab. 2005 Nov;2(5):321-9. doi: 10.1016/j.cmet.2005.09.010.


Protein feeding is known to decrease hunger and subsequent food intake in animals and humans. It has also been suggested that glucose appearance into portal vein, as occurring during meal assimilation, may induce comparable effects. Here, we connect these previous observations by reporting that intestinal gluconeogenesis (i.e., de novo synthesis of glucose) is induced during the postabsorptive time (following food digestion) in rats specifically fed on protein-enriched diet. This results in glucose release into portal blood, counterbalancing the lowering of glycemia resulting from intestinal glucose utilization. Comparable infusions into the portal vein of control postabsorptive rats (fed on starch-enriched diet) decrease food consumption and activate the hypothalamic nuclei regulating food intake. Similar hypothalamic activation occurs on protein feeding. All these effects are absent after denervation of the portal vein. Thus, portal sensing of intestinal gluconeogenesis may be a novel mechanism connecting the macronutrient composition of diet to food intake.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Dietary Carbohydrates
  • Dietary Proteins*
  • Eating*
  • Enzyme Induction
  • Gluconeogenesis*
  • Glucose / metabolism
  • Glucose-6-Phosphatase / biosynthesis*
  • Glutaminase / biosynthesis*
  • Hypothalamus / metabolism
  • Intestine, Small / metabolism*
  • Phosphoenolpyruvate Carboxykinase (GTP) / biosynthesis*
  • Portal Vein / innervation
  • Portal Vein / metabolism
  • Postprandial Period
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Time Factors


  • Dietary Carbohydrates
  • Dietary Proteins
  • Proto-Oncogene Proteins c-fos
  • Glucose-6-Phosphatase
  • Glutaminase
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Glucose