title: Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.
abstract: OBJECTIVE
  To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function.
  
  
  METHODS
  To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting.
  
  
  RESULTS
  We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis.
  
  
  CONCLUSIONS
  Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents.
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Tudurí
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Beiroa
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Porteiro
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Diéguez
authors.affiliation: Instituto de Investigaciones Sanitarias, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Nogueiras
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D059305:Diet, High-Fat; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D006706:Homeostasis / Q000187:drug effects; D054795:Incretins / Q000008:administration & dosage / Q000494:pharmacology; D057967:Infusions, Intraventricular; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: central nervous system; exendin-9; glucagon-like peptide 1; glucose metabolism; islets; β cells