title: Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia.
abstract: Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males. Positron emission tomography was used to determine the effect of GLP-1 on cerebral glucose transport and metabolism during a hyperglycemic clamp with (18)fluoro-deoxy-glucose as tracer. Glucagon-like peptide-1 lowered brain glucose (P=0.023) in all regions. The cerebral metabolic rate for glucose was increased everywhere (P=0.039) but not to the same extent in all regions (P=0.022). The unidirectional glucose transfer across the blood-brain barrier remained unchanged (P=0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased (P=0.013 and 0.017), leading to increased net clearance of the glucose tracer (P=0.006). We show that GLP-1 plays a role in a regulatory mechanism involved in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Gejl
authors.forename: Lærke
authors.initials: L
authors.lastname: Egefjord
authors.forename: Susanne
authors.initials: S
authors.lastname: Lerche
authors.forename: Kim
authors.initials: K
authors.lastname: Vang
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Annette
authors.initials: A
authors.lastname: Mengel
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D020521:Stroke / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
chemical_list: D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; D019788:Fluorodeoxyglucose F18; D052216:Glucagon-Like Peptide 1; D006593:Hexokinase; D005947:Glucose