title: Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.
abstract: Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia.
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; IMDEA Food, CEI UAM+CSIC, Carretera de Cantoblanco 8, Madrid, E-28049, Spain.
authors: Emma
authors: E
authors: Burgos-Ramos
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain.
authors: Sandra
authors: S
authors: Canelles
authors: Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain.
authors: Amaia
authors: A
authors: Rodríguez
authors: Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain.
authors: Javier
authors: J
authors: Gómez-Ambrosi
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain.
authors: Laura M
authors: LM
authors: Frago
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain.
authors: Julie A
authors: JA
authors: Chowen
authors: Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain.
authors: Gema
authors: G
authors: Frühbeck
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain.
authors: Jesús
authors: J
authors: Argente
authors: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain. Electronic address: vicente.barriossa@salud.madrid.org.
authors: Vicente
authors: V
authors: Barrios
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D005947:Glucose
keywords: Glycemia; Glycogen synthesis; Insulin signaling; Leptin; Liver; SH-phosphotyrosine phosphatase 1