%0 Journal Article
%A Álvarez García, Elvira
%A Martínez Ibáñez, María Dolores
%A Roncero Rincón, Isabel
%A Chowen, Julie A.
%A García‐Cuartero, Beatriz
%A Gispert, Juan D.
%A Sanz Miguel, María Del Carmen
%A Vázquez Pérez, Patricia
%A Antonio, Maldonado
%A De Cáceres, Javier
%A Desco, Manuel
%A Pozo García, Miguel Ángel
%A Blázquez Fernández, Enrique
%T The expression of GLP‐1 receptor mRNA and protein allows the effect of GLP‐1 on glucose metabolism in the human hypothalamus and brainstem
%D 2005
%@ 0022-3042
%@ 1471-4159
%U https://hdl.handle.net/20.500.14352/96176
%X In 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.
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