Oscillatory Ca 2+ signaling in glucose-stimulated murine pancreatic β-cells [Elektronisk resurs] Modulation by amino acids, glucagon, caffeine and ryanodine

• Oscillations in cytoplasmic Ca 2+ concentration ([Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] i in isolated mouse β-cells into sustained elevation. Increased Ca 2+ entry promoted the reappearance of the slow [Ca 2+ ] i oscillations. The [Ca 2+ ] 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 [Ca 2+ ] i oscillations due to periodic entry of Ca 2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] 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 Ca 2+ 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 2+ ] i oscillations. Nevertheless, there was an excessive firing of [Ca 2+ ] 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 [Ca 2+ ] 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. 

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Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Cell and Molecular Biology  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska och farmaceutiska grundvetenskaper  (hsv)

Cell- och molekylärbiologi  (hsv)

MEDICINE  (svep)

Morphology, cell biology, pathology  (svep)

Cell biology  (svep)

MEDICIN  (svep)

Morfologi, cellbiologi, patologi  (svep)

Cellbiologi  (svep)

medicinsk cellbiologi  (uu)

Medical Cell Biology  (uu)

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government publication  (marcgt)

Indexterm och SAB-rubrik

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