title: Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans.
abstract: It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc).
authors.affiliation: Neurobiology Research Unit, Department of Neurology, and the PET and Cyclotron Unit, University Hospital, Rigshospitalet,Copenhagen, Denmark. sgh@pet.rh.dk
authors.forename: S G
authors.initials: SG
authors.lastname: Hasselbalch
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: B
authors.initials: B
authors.lastname: Capaldo
authors.forename: A
authors.initials: A
authors.lastname: Postiglione
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
mesh_terms: D000328:Adult; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male
chemical_list: D005947:Glucose