title: The atrial natriuretic peptide and guanylyl cyclase-A system modulates pancreatic beta-cell function.
abstract: Atrial natriuretic peptide (ANP) and its guanylyl cyclase-A (GC-A) receptor are being involved in metabolism, although their role in the endocrine pancreas is still greatly unknown. The aim of this work is to study a possible role for the ANP/GC-A system in modulating pancreatic beta-cell function. The results presented here show a direct effect of the GC-A receptor in regulating glucose-stimulated insulin secretion (GSIS) and beta-cell mass. GC-A activation by its natural ligand, ANP, rapidly blocked ATP-dependent potassium (K(ATP)) channel activity, increased glucose-elicited Ca(2+) signals, and enhanced GSIS in islets of Langerhans. The effect in GSIS was inhibited in islets from GC-A knockout (KO) mice. Pancreatic islets from GC-A KO mice responded to increasing glucose concentrations with enhanced insulin secretion compared with wild type (WT). Remarkably, islets from GC-A KO mice were smaller, presented lower beta-cell mass and decreased insulin content. However, glucose-induced Ca(2+) response was more vigorous in GC-A KO islets, and basal K(ATP) channel activity in GC-A KO beta-cells was greatly diminished compared with WT. When protein levels of the two K(ATP) channel constitutive subunits sulfonylurea receptor 1 and Inward rectifier potassium channel 6.2 were measured, both were diminished in GC-A KO islets. These alterations on beta-cell function were not associated with disruption of glucose tolerance or insulin sensitivity in vivo. Glucose and insulin tolerance tests were similar in WT and GC-A KO mice. Our data suggest that the ANP/GC-A system may have a modulating effect on beta-cell function.
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas andInstituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain. ropero@umh.es
authors.forename: Ana B
authors.initials: AB
authors.lastname: Ropero
authors.forename: Sergi
authors.initials: S
authors.lastname: Soriano
authors.forename: Eva
authors.initials: E
authors.lastname: Tudurí
authors.forename: Laura
authors.initials: L
authors.lastname: Marroquí
authors.forename: Noelia
authors.initials: N
authors.lastname: Téllez
authors.forename: Birgit
authors.initials: B
authors.lastname: Gassner
authors.forename: Pablo
authors.initials: P
authors.lastname: Juan-Picó
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Michaela
authors.initials: M
authors.lastname: Kuhn
authors.forename: Angel
authors.initials: A
authors.lastname: Nadal
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D007328:Insulin; D054086:KATP Channels; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D005947:Glucose