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

Michael Gejl, Lærke Egefjord, Susanne Lerche, Kim Vang, Bo Martin Bibby, Jens Juul Holst, Annette Mengel, Niels Moller, Jorgen Rungby, Birgitte Brock, Albert Gjedde

Research output: Contribution to journalArticle

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 (P0.023) in all regions. The cerebral metabolic rate for glucose was increased everywhere (P0.039) but not to the same extent in all regions (P0.022). The unidirectional glucose transfer across the blood-brain barrier remained unchanged (P0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased (P0.013 and 0.017), leading to increased net clearance of the glucose tracer (P0.006). 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 (US)
Pages (from-to)2146-2152
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 1
Hexokinase
Hyperglycemia
Glucose
Alzheimer Disease
Brain
Stroke
Blood-Brain Barrier
Positron-Emission Tomography
Cross-Over Studies
Type 2 Diabetes Mellitus
Homeostasis
Placebos
Phosphorylation

Keywords

  • 2-deoxy-glucose
  • blood-brain barrier
  • diabetes
  • energy metabolism
  • GLP-1
  • glucagon-like peptide-1
  • glucose
  • pharmacology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia. / Gejl, Michael; Egefjord, Lærke; Lerche, Susanne; Vang, Kim; Bibby, Bo Martin; Holst, Jens Juul; Mengel, Annette; Moller, Niels; Rungby, Jorgen; Brock, Birgitte; Gjedde, Albert.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 12, 12.2012, p. 2146-2152.

Research output: Contribution to journalArticle

Gejl, M, Egefjord, L, Lerche, S, Vang, K, Bibby, BM, Holst, JJ, Mengel, A, Moller, N, Rungby, J, Brock, B & Gjedde, A 2012, 'Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia', Journal of Cerebral Blood Flow and Metabolism, vol. 32, no. 12, pp. 2146-2152. https://doi.org/10.1038/jcbfm.2012.118
Gejl, Michael ; Egefjord, Lærke ; Lerche, Susanne ; Vang, Kim ; Bibby, Bo Martin ; Holst, Jens Juul ; Mengel, Annette ; Moller, Niels ; Rungby, Jorgen ; Brock, Birgitte ; Gjedde, Albert. / Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia. In: Journal of Cerebral Blood Flow and Metabolism. 2012 ; Vol. 32, No. 12. pp. 2146-2152.
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