Glucagon-like-peptide-1 inhibits blood-brain glucose transfer in humans
- Susanne Lerche, MD (lerche{at}ki.au.dk)1,
- Birgitte Brock, MD, PhD1,
- Jørgen Rungby, MD, DMSc1,
- Hans E. Bøtker, MD, DmSc6,
- Niels Møller, MD, DmSc2,
- Anders Rodell, M.Sc., PhD3,
- Bo Martin Bibby, M.Sc., PhD5,
- Jens J. Holst, MD, PhD4,
- Ole Schmitz, MD, DmSc1 and
- Albert Gjedde, MD, DmSc3
- 1Institute of Pharmacology, University of Aarhus, University Park 1240, 8000 Aarhus C
- 2Department of Endocrinology M, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C
- 3PET-Center, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C
- 4Department of Medical Physiology, University of Copenhagen, Panum Institute, Blegdamsvej 3B, 2200 Copenhagen
- 5Department of Biostatistics, University of Aarhus, Vennelyst Park 6, 8000 Aarhus C
- 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
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- Received August 16, 2007.
- Accepted November 3, 2007.
- Copyright © American Diabetes Association
