Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

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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.
Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number12
Pages (from-to)2146-2152
Number of pages7
Publication statusPublished - Dec 2012

    Research areas

  • Adult, Alzheimer Disease, Biological Transport, Blood-Brain Barrier, Brain Chemistry, Brain Ischemia, Cross-Over Studies, Diabetes Mellitus, Type 2, Double-Blind Method, Fluorodeoxyglucose F18, Glucagon-Like Peptide 1, Glucose, Glucose Clamp Technique, Glucose Transporter Type 1, Hexokinase, Humans, Hyperglycemia, Male, Positron-Emission Tomography, Radiopharmaceuticals, Stroke

ID: 44913456