Hypothalamic Integration of Portal Glucose Signals and Control of Food Intake and Insulin Sensitivity

Diabetes Metab. 2010 Sep;36(4):257-62. doi: 10.1016/j.diabet.2010.05.001. Epub 2010 Jun 18.


Glycolysis is an essential metabolic function that lies at the core of any cellular life. Glucose homoeostasis is, thus, a crucial physiological function of living organisms. A system of plasma glucose-sensing in the portal vein plays a key role in this homoeostasis. Connected to the hypothalamus via the peripheral nervous system, the system allows the body to adapt its response to any variation of portal glycaemia. The hypothalamus controls food intake (exogenous glucose supply) and hepatic glycogenolysis (endogenous glucose supply). Intestinal gluconeogenesis, via the release of glucose into the portal vein, plays a key role in the control of hunger and satiety, and of endogenous glucose production through the modulation of liver insulin sensitivity. The induction of intestinal gluconeogenesis provides a physiological explanation for the satiety effects induced by protein-enriched diets. In particular, the influence of protein-enriched diets on the hypothalamus is comparable to the activation observed after glucose infusion into the portal vein. The induction of intestinal gluconeogenesis also offers an explanation for the early improvement in glycaemia control observed in obese diabetic patients treated by gastric-bypass surgery. In addition to intestinal gluconeogenesis, a number of gastrointestinal hormones involved in the control of food intake exert their effects, at least in part, via the peripheral afferent nervous system. These data emphasize the importance of the gut-brain axis in the understanding and treatment of obesity and type 2 diabetes.

Publication types

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

MeSH terms

  • Appetite Regulation*
  • Blood Glucose / metabolism*
  • Blood-Brain Barrier
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / therapy
  • Eating*
  • Gluconeogenesis
  • Glycolysis
  • Humans
  • Hypothalamus / metabolism*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance
  • Intestinal Mucosa / metabolism*
  • Obesity / metabolism
  • Obesity / therapy
  • Portal Vein / metabolism*


  • Blood Glucose
  • Insulin