Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans.
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. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption.


METHODS
We studied 10 healthy men in a randomized, double-blinded, placebo-controlled cross-over experiment. 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 normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer.


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


CONCLUSIONS
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 glycemia, GLP-1 may also protect the brain by limiting intracerebral glucose fluctuation when plasma glucose is increased.
Lerche
Susanne
S
Institute of Pharmacology, University of Aarhus, The Bartholin Building, University Park 1240, 8000 Aarhus C, Denmark. lerche@ki.au.dk
Brock
Birgitte
B
Rungby
Jørgen
J
Bøtker
Hans E
HE
Møller
Niels
N
Rodell
Anders
A
Bibby
Bo Martin
BM
Holst
Jens J
JJ
Schmitz
Ole
O
Gjedde
Albert
A
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010919:Placebos; D049268:Positron-Emission Tomography; D019518:Postprandial Period; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010919:Placebos; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005947:Glucose