title: Dopamine D2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion.
abstract: Dopamine signaling is mediated by five cloned receptors, grouped into D1-like (D1 and D5) and D2-like (D2, D3 and D4) families. We identified by reverse transcription-PCR the presence of dopamine receptors from both families in INS-1E insulin-secreting cells as well as in rodent and human isolated islets. D2 receptor expression was confirmed by immunodetection revealing localization on insulin secretory granules of INS-1E and primary rodent and human beta cells. We then tested potential effects mediated by the identified receptors on beta cell function. Dopamine (10 microM) and the D2-like receptor agonist quinpirole (5 microM) inhibited glucose-stimulated insulin secretion tested in several models, i.e. INS-1E beta cells, fluorescence-activated cell-sorted primary rat beta cells, and pancreatic islets of rat, mouse, and human origin. Insulin exocytosis is controlled by metabolism coupled to cytosolic calcium changes. Measurements of glucose-induced mitochondrial hyperpolarization and ATP generation showed that dopamine and D2-like agonists did not inhibit glucose metabolism. On the other hand, dopamine decreased cell membrane depolarization as well as cytosolic calcium increases evoked by glucose stimulation in INS-1E beta cells. These results show for the first time that dopamine receptors are expressed in pancreatic beta cells. Dopamine inhibited glucose-stimulated insulin secretion, an effect that could be ascribed to D2-like receptors. Regarding the molecular mechanisms implicated in dopamine-mediated inhibition of insulin release, our results point to distal steps in metabolism-secretion coupling. Thus, the role played by dopamine in glucose homeostasis might involve dopamine receptors, expressed in pancreatic beta cells, modulating insulin release.
authors.affiliation: Department of Cell Physiology and Metabolism, University Medical Center, Geneva University Hospitals, CH-1211 Geneva 4, Switzerland. rubiweiss@yahoo.com
authors.forename: Blanca
authors.initials: B
authors.lastname: Rubí
authors.forename: Sanda
authors.initials: S
authors.lastname: Ljubicic
authors.forename: Shirin
authors.initials: S
authors.lastname: Pournourmohammadi
authors.forename: Stefania
authors.initials: S
authors.lastname: Carobbio
authors.forename: Mathieu
authors.initials: M
authors.lastname: Armanet
authors.forename: Clarissa
authors.initials: C
authors.lastname: Bartley
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005089:Exocytosis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D018491:Dopamine Agonists; D007328:Insulin; D007329:Insulin Antagonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D005947:Glucose; D002118:Calcium; D004298:Dopamine