title: Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study.
abstract: We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are.
  
  
  METHODS
  Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics.
  
  
  RESULTS
  Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus.
  
  
  CONCLUSIONS
  Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.
authors.affiliation: Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Malte F
authors.initials: MF
authors.lastname: Alf
authors.forename: João M N
authors.initials: JM
authors.lastname: Duarte
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D049268:Positron-Emission Tomography
chemical_list: D007328:Insulin; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: Michaelis–Menten kinetics; brain glucose metabolism; hypoglycemia; positron-emission tomography