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Oscillatory Ca<sup>2+</sup> signaling in glucose-stimulated murine pancreatic β-cells : Modulation by amino acids, glucagon, caffeine and ryanodine

<p>Oscillations in cytoplasmic Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca<sup>2+</sup>]<sub> i</sub>. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca<sup>2+</sup>]<sub> i</sub> oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca<sup>2+</sup>]<sub> i</sub> in isolated mouse β-cells into sustained elevation. Increased Ca<sup>2+</sup> entry promoted the reappearance of the slow [Ca<sup>2+</sup>]<sub> i</sub> oscillations. The [Ca<sup>2+</sup>]<sub> i</sub> oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca<sup>2+</sup>]<sub> i</sub> oscillations due to periodic entry of Ca<sup>2+</sup> as well as with transients evoked by mobilization of intracellular stores. The [Ca<sup>2+</sup>]<sub> i</sub> oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca<sup>2+</sup>]<sub> i</sub> were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca<sup>2+</sup>]<sub> i</sub> transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca<sup>2+</sup> release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca<sup>2+</sup>]<sub> i</sub> oscillations. Nevertheless, there was an excessive firing of [Ca<sup>2+</sup>]<sub> i</sub> transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca<sup>2+</sup>]<sub> i</sub> transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.</p>

Identiferoai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-1408
Date January 2001
CreatorsAhmed, Meftun
PublisherUppsala University, Department of Medical Cell Biology, Uppsala : Acta Universitatis Upsaliensis
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeDoctoral thesis, comprehensive summary, text
RelationComprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1064

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