The rate-limiting step for glucose transport into the hypothalamus is across the blood-hypothalamus interface

J Neurochem. 2009 May;109 Suppl 1(Suppl 1):38-45. doi: 10.1111/j.1471-4159.2009.05934.x.

Abstract

Specialized glucosensing neurons are present in the hypothalamus, some of which neighbor the median eminence, where the blood-brain barrier has been reported leaky. A leaky blood-brain barrier implies high tissue glucose levels and obviates a role for endothelial glucose transporters in the control of hypothalamic glucose concentration, important in understanding the mechanisms of glucose sensing We therefore addressed the question of blood-brain barrier integrity at the hypothalamus for glucose transport by examining the brain tissue-to-plasma glucose ratio in the hypothalamus relative to other brain regions. We also examined glycogenolysis in hypothalamus because its occurrence is unlikely in the potential absence of a hypothalamus-blood interface. Across all regions the concentration of glucose was comparable at a given plasma glucose concentration and was a near linear function of plasma glucose. At steady-state, hypothalamic glucose concentration was similar to the extracellular hypothalamic glucose concentration reported by others. Hypothalamic glycogen fell at a rate of approximately 1.5 micromol/g/h and remained present in substantial amounts. We conclude for the hypothalamus, a putative primary site of brain glucose sensing that: the rate-limiting step for glucose transport into brain cells is at the blood-hypothalamus interface, and that glycogenolysis is consistent with a substantial blood -to- intracellular glucose concentration gradient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Biological Transport, Active / physiology
  • Blood Glucose / metabolism
  • Blood-Brain Barrier / physiology*
  • Brain / anatomy & histology
  • Brain Chemistry / physiology
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / metabolism*
  • Glycogen / metabolism
  • Hypothalamus / metabolism*
  • Kinetics
  • Liver Glycogen / metabolism
  • Male
  • Microwaves
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tissue Fixation

Substances

  • Blood Glucose
  • Glucose Transporter Type 1
  • Liver Glycogen
  • Slc2a1 protein, rat
  • Glycogen
  • Glucose