Glucagon-like-peptide-1 inhibits blood-brain glucose transfer in humans

  1. Susanne Lerche, MD (lerche{at}ki.au.dk)1,
  2. Birgitte Brock, MD, PhD1,
  3. Jørgen Rungby, MD, DMSc1,
  4. Hans E. Bøtker, MD, DmSc6,
  5. Niels Møller, MD, DmSc2,
  6. Anders Rodell, M.Sc., PhD3,
  7. Bo Martin Bibby, M.Sc., PhD5,
  8. Jens J. Holst, MD, PhD4,
  9. Ole Schmitz, MD, DmSc1 and
  10. Albert Gjedde, MD, DmSc3
  1. 1Institute of Pharmacology, University of Aarhus, University Park 1240, 8000 Aarhus C
  2. 2Department of Endocrinology M, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C
  3. 3PET-Center, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C
  4. 4Department of Medical Physiology, University of Copenhagen, Panum Institute, Blegdamsvej 3B, 2200 Copenhagen
  5. 5Department of Biostatistics, University of Aarhus, Vennelyst Park 6, 8000 Aarhus C
  6. 6Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, 8200 Aarhus N

    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.

    Hypothesis, Research design and Methods: To test whether these neuroprotective effects could relate to changes of glucose transport and consumption we studied 10 healthy men in a randomized, double-blinded placebo-controlled cross-over experimental design. 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 normoglycaemic (plasma glucose ≈ 4.5mM) clamp with 18-fluoro-deoxy-glucose (FDG) as tracer.

    Results: On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral grey matter (P=0.05) and by 25-30% in individual grey matter regions (P=0.02-0.06). The same regions revealed a uniform trend towards similarly reduced cerebral glucose metabolism. Consequently, the intracerebral glucose concentration remained constant in all regions, with and without GLP-1.

    Conclusions: Therefore 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 glycaemia, GLP-1 may also protect the brain by limiting intracerebral glucose fluctuation when the plasma glucose is increased.

    Footnotes

      • Received August 16, 2007.
      • Accepted November 3, 2007.

    This Article

    1. Published online before print November 8, 2007, doi: 10.2337/db07-1162
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