TY - JOUR

T1 - Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

AU - Lerche, Susanne

AU - Brock, Birgitte

AU - Rungby, Jørgen

AU - Bøtker, Hans E

AU - Møller, Niels

AU - Rodell, Anders

AU - Bibby, Bo Martin

AU - Holst, Jens J

AU - Schmitz, Ole

AU - Gjedde, Albert

N1 - Keywords: Adult; Biological Transport; Blood Glucose; Blood-Brain Barrier; Brain; C-Peptide; Double-Blind Method; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Male; Placebos; Positron-Emission Tomography; Postprandial Period; Recombinant Proteins; Reference Values

PY - 2008

Y1 - 2008

N2 - 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 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.

AB - 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 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.

U2 - 10.2337/db07-1162

DO - 10.2337/db07-1162

M3 - Journal article

C2 - 17991759

VL - 57

SP - 325

EP - 331

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -