Abstract
Background and Aims: Glucagon-like-peptide-1 (GLP-1) has many effects
regarding glucose homeostasis. GLP-1 receptors are broadly represented in
the brain. Recent research in rodents has suggested a potentially protective
effect of GLP-1 in the brain. The mechanism behind this effect is unknown.
The possible role of GLP-1 in the human brain glucose metabolism is not well
characterized. To gain more insight into changes of glucose delivery and/or
metabolism, which may explain neuroprotective effects, we explored glucose
transport and consumption in 10 healthy men in a randomized, doubleblinded
placebo-controlled cross-over experimental design.
Materials and Methods: The acute effect (independent of insulin) of GLP-
1 on glucose uptake in the brain was visualized by Positron Emission
Tomography (PET) during a pituitary-pancreatic normoglycaemic (plasma
glucose § 4.5mM) clamp with 18-fluoro-deoxy-glucose (FDG) as a tracer of
glucose.
Results: The insulin infusion rate was 0.12mU/kg/min, growth hormone
and glucagon were replaced to baseline levels. Intact GLP-1 levels were 51± 3
(mean ± SEM) vs. 0.95 ± 0.1pmol/l (GLP-1 vs. placebo). In total cerebral grey
matter, GLP-1 reduced cerebral glucose uptake by 30%, 0.99 micromol/cm3/
min ± 0.09 (placebo) vs. 0.70 ± 0.04 (GLP-1) (P=0.05). In the cerebral cortex,
reduction was 29%, 0.98 ± 0.09 vs. 0.69 ± 0.04 (P=0.06), in white matter 26%,
0.50 ± 0.04 vs. 0.37 ± 0.02 (P=0.03), in thalamus 31%, 1.11 ± 0.12 vs. 0.77
± 0.06 (P=0.05), in striatum 28%, 0.98 ± 0.09 vs. 0.70 ± 0.05 (P=0.06), in
cerebellar cortex 30%, 1.12 ± 0.12 vs. 0.82 ± 0.06 (P=0.06) and in brainstem
33%, 0.76 ± 0.07 vs. 0.50 ± 0.03 (P=0.02). The same regions showed a uniform
trend towards reduced cerebral glucose metabolism. As a result, the intra
cerebral glucose concentration remained the same in all regions, with and
without GLP-1.
Conclusion: For the first time, we demonstrate that a hormone involved in
postprandial glucose regulation also limits glucose delivery to brain tissue
and hence provides a possible explanation for the connection between plasma
glucose and brain glucose regulation. As GLP-1 reduces glucose uptake across
the intact blood brain barrier at normal glycaemia, GLP-1 may also protect
the brain by limiting intra cerebral glucose fluctuation when plasma glucose
is increased.
regarding glucose homeostasis. GLP-1 receptors are broadly represented in
the brain. Recent research in rodents has suggested a potentially protective
effect of GLP-1 in the brain. The mechanism behind this effect is unknown.
The possible role of GLP-1 in the human brain glucose metabolism is not well
characterized. To gain more insight into changes of glucose delivery and/or
metabolism, which may explain neuroprotective effects, we explored glucose
transport and consumption in 10 healthy men in a randomized, doubleblinded
placebo-controlled cross-over experimental design.
Materials and Methods: The acute effect (independent of insulin) of GLP-
1 on glucose uptake in the brain was visualized by Positron Emission
Tomography (PET) during a pituitary-pancreatic normoglycaemic (plasma
glucose § 4.5mM) clamp with 18-fluoro-deoxy-glucose (FDG) as a tracer of
glucose.
Results: The insulin infusion rate was 0.12mU/kg/min, growth hormone
and glucagon were replaced to baseline levels. Intact GLP-1 levels were 51± 3
(mean ± SEM) vs. 0.95 ± 0.1pmol/l (GLP-1 vs. placebo). In total cerebral grey
matter, GLP-1 reduced cerebral glucose uptake by 30%, 0.99 micromol/cm3/
min ± 0.09 (placebo) vs. 0.70 ± 0.04 (GLP-1) (P=0.05). In the cerebral cortex,
reduction was 29%, 0.98 ± 0.09 vs. 0.69 ± 0.04 (P=0.06), in white matter 26%,
0.50 ± 0.04 vs. 0.37 ± 0.02 (P=0.03), in thalamus 31%, 1.11 ± 0.12 vs. 0.77
± 0.06 (P=0.05), in striatum 28%, 0.98 ± 0.09 vs. 0.70 ± 0.05 (P=0.06), in
cerebellar cortex 30%, 1.12 ± 0.12 vs. 0.82 ± 0.06 (P=0.06) and in brainstem
33%, 0.76 ± 0.07 vs. 0.50 ± 0.03 (P=0.02). The same regions showed a uniform
trend towards reduced cerebral glucose metabolism. As a result, the intra
cerebral glucose concentration remained the same in all regions, with and
without GLP-1.
Conclusion: For the first time, we demonstrate that a hormone involved in
postprandial glucose regulation also limits glucose delivery to brain tissue
and hence provides a possible explanation for the connection between plasma
glucose and brain glucose regulation. As GLP-1 reduces glucose uptake across
the intact blood brain barrier at normal glycaemia, GLP-1 may also protect
the brain by limiting intra cerebral glucose fluctuation when plasma glucose
is increased.
Originalsprog | Engelsk |
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Publikationsdato | 2007 |
Antal sider | 1 |
Status | Udgivet - 2007 |
Udgivet eksternt | Ja |
Begivenhed | 43rd EASD Annual Meeting of the European Association for the Study of Diabetes - Amsterdam, Holland Varighed: 18 jun. 2007 → 21 sep. 2007 |
Konference
Konference | 43rd EASD Annual Meeting of the European Association for the Study of Diabetes |
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Land/Område | Holland |
By | Amsterdam |
Periode | 18/06/2007 → 21/09/2007 |