TY - JOUR

T1 - The effects of incretin hormones on cerebral glucose metabolism in health and disease

AU - Nilsson, Malin

AU - Gjedde, Albert

AU - Brock, Birgitte

AU - Gejl, Michael

AU - Rungby, Jørgen

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia. GLP-1, when administered as long-acting analogues or intravenously, appears to decrease transport of glucose in normoglycaemic conditions, without affecting the total cerebral glucose content. During hypoglycaemia this effect seems abated, whereas during hyperglycaemia GLP-1 regulates cerebral glucose metabolism towards stable levels resembling normoglycaemia. In Alzheimer's disease, a 6-month intervention with GLP-1 maintained cerebral glucose levels at baseline levels, contrasting the decline otherwise seen in Alzheimer's. Kinetic studies suggest blood-brain barrier (BBB) glucose transport as the key player in GLP-1 mediated effects on cerebral glucose metabolism. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

AB - Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia. GLP-1, when administered as long-acting analogues or intravenously, appears to decrease transport of glucose in normoglycaemic conditions, without affecting the total cerebral glucose content. During hypoglycaemia this effect seems abated, whereas during hyperglycaemia GLP-1 regulates cerebral glucose metabolism towards stable levels resembling normoglycaemia. In Alzheimer's disease, a 6-month intervention with GLP-1 maintained cerebral glucose levels at baseline levels, contrasting the decline otherwise seen in Alzheimer's. Kinetic studies suggest blood-brain barrier (BBB) glucose transport as the key player in GLP-1 mediated effects on cerebral glucose metabolism. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

U2 - 10.1016/j.neuropharm.2017.12.031

DO - 10.1016/j.neuropharm.2017.12.031

M3 - Review

C2 - 29274367

VL - 136

SP - 243

EP - 250

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - Part B

ER -