Oscillatory Ca²⁺ signaling in glucose-stimulated murine pancreatic β-cells : Modulation by amino acids, glucagon, caffeine and ryanodine

Description

<p>Oscillations in cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) 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 [Ca²⁺]_i. 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 [Ca²⁺]_i 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 [Ca²⁺]_i in isolated mouse β-cells into sustained elevation. Increased Ca²⁺ entry promoted the reappearance of the slow [Ca²⁺]_i oscillations. The [Ca²⁺]_i 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 [Ca²⁺]_i oscillations due to periodic entry of Ca²⁺ as well as with transients evoked by mobilization of intracellular stores. The [Ca²⁺]_i 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 [Ca²⁺]_i 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 [Ca²⁺]_i 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 Ca²⁺ 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 [Ca²⁺]_i oscillations. Nevertheless, there was an excessive firing of [Ca²⁺]_i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca²⁺]_i 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>

Links & Downloads

1. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1408
2. ISBN 91-554-5084-9

Tags

Cell biology

pancreatic β-cells

islets of Langerhans

glucose

Ca2+ oscillations

Ca2+ transients

potassium

ryanodine

caffeine

glucagon

cAMP

inositol 1

4

5-trisphosphate

fura-2

glycine

alanine

arginine

Ca2+ channels

rats

lean mice

ob/ob mice

leptin

Cellbiologi

Cell biology

Cellbiologi

Additional Fields

Identifer	oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-1408
Date	January 2001
Creators	Ahmed, Meftun
Publisher	Uppsala University, Department of Medical Cell Biology, Uppsala : Acta Universitatis Upsaliensis
Source Sets	DiVA Archive at Upsalla University
Language	English
Detected Language	English
Type	Doctoral thesis, comprehensive summary, text
Relation	Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1064