Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors

dc.creatorTuduri, E
dc.creatorFiliputti, E
dc.creatorCarneiro, EM
dc.creatorQuesada, I
dc.date2008
dc.dateMAY
dc.date2014-08-01T18:32:53Z
dc.date2015-11-26T17:59:49Z
dc.date2014-08-01T18:32:53Z
dc.date2015-11-26T17:59:49Z
dc.date.accessioned2018-03-29T00:42:12Z
dc.date.available2018-03-29T00:42:12Z
dc.identifierAmerican Journal Of Physiology-endocrinology And Metabolism. Amer Physiological Soc, v. 294, n. 5, n. E952, n. E960, 2008.
dc.identifier0193-1849
dc.identifierWOS:000255501600018
dc.identifier10.1152/ajpendo.00641.2007
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/80569
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/80569
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1291784
dc.descriptionGlucagon secreted from pancreatic alpha-cells plays a critical role in glycemia, mainly by hepatic glucose mobilization. In diabetic patients, an impaired control of glucagon release can worsen glucose homeostasis. Despite its importance, the mechanisms that regulate its secretion are still poorly understood. Since alpha-cells are particularly sensitive to neural and paracrine factors, in this report we studied the role of purinergic receptors and extracellular ATP, which can be released from nerve terminals and beta-cell secretory granules. Using immunocytochemistry, we identified in alpha-cells the P2 receptor subtype P2Y(1), as well as the P1 receptors A(1) and A(2A). In contrast, only P2Y(1) and A(1) receptors were localized in beta-cells. To analyze the role of purinergic receptors in alpha-cell function, we studied their participation in Ca2+ signaling. At low glucose concentrations, mouse alpha-cells exhibited the characteristic oscillatory Ca2+ signals that lead to secretion. Application of ATP (1-10 mu M) abolished these oscillations or reduced their frequency in alpha-cells within intact islets and isolated in culture. ATP gamma S, a nonhydrolyzable ATP derivative, indicated that the ATP effect was mainly direct rather than through ATP-hydrolytic products. Additionally, adenosine (1-10 mu M) was also found to reduce Ca2+ signals. ATP-mediated inhibition of Ca2+ signaling was accompanied by a decrease in glucagon release from intact islets in contrast to the adenosine effect. Using pharmacological agonists, we found that only P2Y(1) and A(2A) were likely involved in the inhibitory effect on Ca2+ signaling. All these findings indicate that extracellular ATP and purinergic stimulation are effective regulators of the alpha-cell function.
dc.descriptiono TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.
dc.description294
dc.description5
dc.descriptionE952
dc.descriptionE960
dc.languageen
dc.publisherAmer Physiological Soc
dc.publisherBethesda
dc.publisherEUA
dc.relationAmerican Journal Of Physiology-endocrinology And Metabolism
dc.relationAm. J. Physiol.-Endocrinol. Metab.
dc.rightsembargo
dc.sourceWeb of Science
dc.subjectconfocal microscopy
dc.subjectislets
dc.subjectparacrine communication
dc.subjectStimulated Insulin-release
dc.subjectBeta-cells
dc.subjectPostprandial Hyperglycemia
dc.subjectDelta-cells
dc.subjectAdenine-nucleotides
dc.subjectEndocrine Pancreas
dc.subjectIdentified Alpha
dc.subjectIntact Islets
dc.subjectGlucose
dc.subjectLangerhans
dc.titleInhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors
dc.typeArtículos de revistas


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