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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 294/5/E952    most recent 00641.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tudurí, E. Articles by Quesada, I. PubMed PubMed Citation Articles by Tudurí, E. Articles by Quesada, I.

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

¹Institute of Bioengineering, Miguel Hernandez University, Elche, Spain; ²CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Spain; and ³Department of Physiology and Biophysics, Institute of Biology, Unicamp, Campinas São Paulo, São Paulo, Brazil

Submitted 3 October 2007 ; accepted in final form 14 March 2008

Glucagon secreted from pancreatic -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 -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 β-cell secretory granules. Using immunocytochemistry, we identified in -cells the P2 receptor subtype P2Y₁, as well as the P1 receptors A₁ and A_2A. In contrast, only P2Y₁ and A₁ receptors were localized in β-cells. To analyze the role of purinergic receptors in -cell function, we studied their participation in Ca²⁺ signaling. At low glucose concentrations, mouse -cells exhibited the characteristic oscillatory Ca²⁺ signals that lead to secretion. Application of ATP (1–10 µM) abolished these oscillations or reduced their frequency in -cells within intact islets and isolated in culture. ATPS, a nonhydrolyzable ATP derivative, indicated that the ATP effect was mainly direct rather than through ATP-hydrolytic products. Additionally, adenosine (1–10 µM) 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 P2Y₁ 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 -cell function.

confocal microscopy; islets; paracrine communication