RT Journal Article
T1 The expression of GLP‐1 receptor mRNA and protein allows the effect of GLP‐1 on glucose metabolism in the human hypothalamus and brainstem
A1 Álvarez García, Elvira
A1 Martínez Ibáñez, María Dolores
A1 Roncero Rincón, Isabel
A1 Chowen, Julie A.
A1 García‐Cuartero, Beatriz
A1 Gispert, Juan D.
A1 Sanz Miguel, María Del Carmen
A1 Vázquez Pérez, Patricia
A1 Antonio, Maldonado
A1 De Cáceres, Javier
A1 Desco, Manuel
A1 Pozo García, Miguel Ángel
A1 Blázquez Fernández, Enrique
AB 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.
SN 0022-3042
SN 1471-4159
YR 2005
FD 2005
LK https://hdl.handle.net/20.500.14352/96176
UL https://hdl.handle.net/20.500.14352/96176
LA eng
NO Alvarez 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.x
DS Docta Complutense
RD 20 jul 2024