Person:
Blázquez Fernández, Enrique

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First Name
Enrique
Last Name
Blázquez Fernández
URI
https://hdl.handle.net/20.500.14352/82765
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Area
Bioquímica y Biología Molecular
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2001 - 20053
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Author: Chowen, Julie A. × Subject: 612.017 ×

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Now showing 1 - 3 of 3
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    Evidence that glucokinase regulatory protein is expressed 
and interacts with glucokinase in rat brain
    (Journal of Neurochemistry, 2001) Chowen, Julie A.; Vázquez Pérez, Patricia; Álvarez García, Elvira; Roncero Rincón, Isabel; Blázquez Fernández, Enrique; Wiley
    Our previous description of functional glucokinase isoforms in the rat brain has opened new questions concerning the presence of glucokinase regulatory protein in the brain and the functional role of its interactions with glucokinase. In this study, we found glucokinase regulatory protein mRNA in rat brain, pancreatic islets and liver. In addition, we found two other variant splicing isoforms, both identified in hypothalamus, pancreatic islets and liver. In situ hybridization studies revealed the presence of glucokinase regulatory protein mRNA, the highest number of positive cells being found in the paraventricular nucleus of the hypothalamus. Glucokinase regulatory protein gene expression gave rise to a protein of 69 kDa mainly in nuclear and soluble cell fractions. Glutathione S-transferase protein fused either to rat liver or human pancreatic islet glucokinase were able to precipitate glucokinase regulatory protein from liver or hypothalamic extracts in the presence of fructose-6-phosphate, the amount of protein co-precipitated being decreased with fructose-1-phosphate. These findings suggest that the presence of glucokinase and glucokinase regulatory protein in the rat brain would facilitate the adaptation of this organ to fluctuations in blood glucose concentrations, and both proteins may participate in glucose-sensing and metabolic regulation in the central nervous system.
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    Expression of glucose transporter isoform GLUT‐2 and glucokinase genes in human brain
    (Journal of Neurochemistry, 2004) Chowen, Julie A.; Rábano, Alberto; Vázquez Pérz, Patricia; Roncero Rincón, Isabel; Álvarez García, Elvira; Sanz Miguel, María Del Carmen; Blázquez Fernández, Enrique; Wiley
    The glucose transporter isoform-2 (GLUT-2) and glucokinase are considered to be components of a glucose sensor system controlling several key processes, and hence may modulate feeding behaviour. We have found GLUT-2 and glucokinase mRNAs in several brain regions, including the ventromedial and arcuate nuclei of the hypothalamus. GLUT-2, glucokinase and glucokinase regulatory protein mRNAs and proteins were present in these areas as determined by biochemical approaches. In addition, glucose-phosphorylating activity with a high apparent Km for glucose that displayed no product inhibition by glucose-6-phosphate was observed. Increased glycaemia after meals may be recognized by specific hypothalamic neurones due to the high Km of GLUT-2 and glucokinase. This enzyme is considered to be the true glucose sensor because it catalyses the rate-limiting step of glucose catabolism its activity being regulated by interaction with glucokinase regulatory protein, that functions as a metabolic sensor
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    The expression of GLP‐1 receptor mRNA and protein allows the effect of GLP‐1 on glucose metabolism in the human hypothalamus and brainstem
    (Journal of Neurochemistry, 2005) Álvarez García, Elvira; Martínez Ibáñez, María Dolores; Roncero Rincón, Isabel; Chowen, Julie A.; García Cuartero, Beatriz; Gispert, Juan D.; Sanz Miguel, María Del Carmen; Vázquez Pérez, Patricia; Antonio, Maldonado; De Cáceres, Javier; Desco, Manuel; Pozo García, Miguel Ángel; Blázquez Fernández, Enrique
    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.