title: Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption.
  
  
  METHODS
  We studied 10 healthy men in a randomized, double-blinded, placebo-controlled cross-over experiment. We used positron emission tomography to determine the acute insulin-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitary-pancreatic normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer.
  
  
  RESULTS
  On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P = 0.05) and by 25-30% in individual gray matter regions (P = 0.02-0.06). The same regions revealed a uniform trend toward similarly reduced cerebral glucose metabolism. Consequently, the intracerebral glucose concentration remained constant in all regions, with and without GLP-1.
  
  
  CONCLUSIONS
  We have demonstrated that a hormone involved in postprandial glucose regulation also limits glucose delivery to brain tissue and hence provides a possible regulatory mechanism for the link between plasma glucose and brain glucose. Because GLP-1 reduces glucose uptake across the intact blood-brain barrier at normal glycemia, GLP-1 may also protect the brain by limiting intracerebral glucose fluctuation when plasma glucose is increased.
authors.affiliation: Institute of Pharmacology, University of Aarhus, The Bartholin Building, University Park 1240, 8000 Aarhus C, Denmark. lerche@ki.au.dk
authors.forename: Susanne
authors.initials: S
authors.lastname: Lerche
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
authors.forename: Hans E
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Anders
authors.initials: A
authors.lastname: Rodell
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010919:Placebos; D049268:Positron-Emission Tomography; D019518:Postprandial Period; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010919:Placebos; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005947:Glucose