Álvarez García, ElviraMartínez Ibáñez, María DoloresRoncero Rincón, IsabelChowen, Julie A.García‐Cuartero, BeatrizGispert, Juan D.Sanz Miguel, María Del CarmenVázquez Pérez, PatriciaAntonio, MaldonadoDe Cáceres, JavierDesco, ManuelPozo García, Miguel ÁngelBlázquez Fernández, Enrique2024-01-292024-01-292005Alvarez E, Martínez MD, Roncero I, et al. The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem. J Neurochem. 2005;92(4):798-806. doi:10.1111/j.1471-4159.2004.02914.x0022-30421471-415910.1111/j.1471-4159.2004.02914.xhttps://hdl.handle.net/20.500.14352/96176In the present work, several experimental approaches were used to determine the presence of the glucagon-like peptide-1 receptor (GLP-1R) and the biological actions of its ligand in the human brain. In situ hybridization histochemistry revealed specific labelling for GLP-1 receptor mRNA in several brain areas. In addition, GLP-1R, glucose transporter isoform (GLUT-2) and glucokinase (GK) mRNAs were identified in the same cells, especially in areas of the hypothalamus involved in feeding behaviour. GLP-1R gene expression in the human brain gave rise to a protein of 56 kDa as determined by affinity cross-linking assays. Specific binding of 125I-GLP-1(7-36) amide to the GLP-1R was detected in several brain areas and was inhibited by unlabelled GLP-1(7-36) amide, exendin-4 and exendin (9-39). A further aim of this work was to evaluate cerebral-glucose metabolism in control subjects by positron emission tomography (PET), using 2-[F-18] deoxy-D-glucose (FDG). Statistical analysis of the PET studies revealed that the administration of GLP-1(7-36) amide significantly reduced (p < 0.001) cerebral glucose metabolism in hypothalamus and brainstem. Because FDG-6-phosphate is not a substrate for subsequent metabolic reactions, the lower activity observed in these areas after peptide administration may be due to reduction of the glucose transport and/or glucose phosphorylation, which should modulate the glucose sensing process in the GLUT-2- and GK-containing cells.engAttribution 4.0 Internationaljournal articlehttps://doi.org/10.1111/j.1471-4159.2004.02914.xopen access612.017Biological effectsGene expressionGlucagon-likepeptide-1 receptorGlucose sensingHuman brainCiencias Biomédicas24 Ciencias de la Vida