title: The rate-limiting step for glucose transport into the hypothalamus is across the blood-hypothalamus interface.
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.
authors.affiliation: Institute of Physics for Complex Matter, Centre d'Imagerie Biomédicale (CIBM), Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. carole.poitry-yamate@epfl.ch
authors.forename: Carol
authors.initials: C
authors.lastname: Poitry-Yamate
authors.forename: HongXia
authors.initials: H
authors.lastname: Lei
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007700:Kinetics; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008872:Microwaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D016707:Tissue Fixation
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D008112:Liver Glycogen; C495679:Slc2a1 protein, rat; D006003:Glycogen; D005947:Glucose