Global vs. regional differences in resting glucose metabolism across brain states

G.J. Thompson; K.N. Mortensen; A. Gjedde; P. Herman; M.J. Parent; D.L. Rothman; R. Kupers; M. Ptito; J. Stender; S. Laureys; V. Riedl; M.T. Alkire; F. Hyder

doi:10.1177/0271678X17695982

Global vs. regional differences in resting glucose metabolism across brain states

G.J. Thompson, K.N. Mortensen, A. Gjedde, P. Herman, M.J. Parent, D.L. Rothman, R. Kupers, M. Ptito, J. Stender, S. Laureys, V. Riedl, M.T. Alkire, F. Hyder

Institut for Neurovidenskab

1 Citationer (Scopus)

Abstract

Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

Originalsprog	Engelsk
Artikelnummer	PS01-081
Tidsskrift	Journal of Cerebral Blood Flow and Metabolism
Vol/bind	37
Udgave nummer	1 suppl
Sider (fra-til)	96-168
Antal sider	71
ISSN	0271-678X
DOI	https://doi.org/10.1177/0271678X17695982
Status	Udgivet - 2017

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10.1177/0271678X17695982

Citationsformater

Thompson, G. J., Mortensen, K. N., Gjedde, A., Herman, P., Parent, M. J., Rothman, D. L., Kupers, R., Ptito, M., Stender, J., Laureys, S., Riedl, V., Alkire, M. T., & Hyder, F. (2017). Global vs. regional differences in resting glucose metabolism across brain states. Journal of Cerebral Blood Flow and Metabolism, 37(1 suppl), 96-168. [PS01-081]. https://doi.org/10.1177/0271678X17695982

Thompson, GJ, Mortensen, KN, Gjedde, A, Herman, P, Parent, MJ, Rothman, DL, Kupers, R , Ptito, M, Stender, J, Laureys, S, Riedl, V, Alkire, MT & Hyder, F 2017, 'Global vs. regional differences in resting glucose metabolism across brain states', Journal of Cerebral Blood Flow and Metabolism, bind 37, nr. 1 suppl, PS01-081, s. 96-168. https://doi.org/10.1177/0271678X17695982

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title = "Global vs. regional differences in resting glucose metabolism across brain states",

abstract = "Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.",

author = "G.J. Thompson and K.N. Mortensen and A. Gjedde and P. Herman and M.J. Parent and D.L. Rothman and R. Kupers and M. Ptito and J. Stender and S. Laureys and V. Riedl and M.T. Alkire and F. Hyder",

year = "2017",

doi = "10.1177/0271678X17695982",

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T1 - Global vs. regional differences in resting glucose metabolism across brain states

AU - Thompson, G.J.

AU - Mortensen, K.N.

AU - Gjedde, A.

AU - Herman, P.

AU - Parent, M.J.

AU - Rothman, D.L.

AU - Kupers, R.

AU - Ptito, M.

AU - Stender, J.

AU - Laureys, S.

AU - Riedl, V.

AU - Alkire, M.T.

AU - Hyder, F.

PY - 2017

Y1 - 2017

N2 - Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

AB - Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

U2 - 10.1177/0271678X17695982

DO - 10.1177/0271678X17695982

M3 - Conference abstract in journal

C2 - 28366130

SN - 0271-678X

VL - 37

SP - 96

EP - 168

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 1 suppl

M1 - PS01-081

ER -

Global vs. regional differences in resting glucose metabolism across brain states

Abstract

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