title: No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.
abstract: The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transport and cerebral metabolism (CMRglc) was studied using the intravenous double-indicator method and positron emission tomography using [18F]fluorodeoxyglucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/- 4 years old) were studied twice during a euglycemic and a euglycemic-hyperinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose. During insulin infusion, arterial plasma insulin levels increased from 48.5 to 499.4 pmol/l. The permeability-surface area products for glucose and FDG BBB transport obtained with the double-indicator method remained constant during hyperinsulinemia. Similarly using PET-FDG, no changes were observed in the unidirectional clearance of FDG from blood to brain. k2* (FDG transport from brain to blood) increased significantly by 15 and 18% (gray and white matter, respectively), and k4* (dephosphorylation of FDG) increased by 18%. The increase in k2* may be caused by insulin inducing a decrease in the available FDG brain pool. The increase in k4* may be related to an increased loss of labeled products during insulin fusion. Irrespective of these changes, CMRglc remained unchanged in all brain regions. We conclude that hyperinsulinemia within the normal physiologic range does not affect BBB glucose transport or net cerebral glucose metabolism.
authors.affiliation: Department of Neurology, University Hospital, Rigshospitalet, Copenhagen, Denmark. s.hasselbalch@dadlnet.dk
authors.forename: S G
authors.initials: SG
authors.lastname: Hasselbalch
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: C
authors.initials: C
authors.lastname: Videbaek
authors.forename: L H
authors.initials: LH
authors.lastname: Pinborg
authors.forename: J F
authors.initials: JF
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Holm
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
mesh_terms: D000328:Adult; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D010539:Permeability; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18