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

Susanne Lerche, Birgitte Brock, Jørgen Rungby, Hans E. Bøtker, Niels Møller, Anders Rodell, Bo Martin Bibby, Jens J. Holst, Ole Schmitz, Albert Gjedde

Research output: Contribution to journalArticlepeer-review

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. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption. RESEARCH DESIGN AND 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 ∼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.

Original languageEnglish (US)
Pages (from-to)325-331
Number of pages7
JournalDiabetes
Volume57
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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