Cell-specific Ca2+ responses in glucose-stimulated single and aggregated β-cells

A rise in the cytoplasmic calcium concentration ([Ca2+](i)) is a key event for insulin exocytosis. We have recently found that the 'early [Ca2+](i) response' in single ob/ob mouse beta-cells is reproduced during consecutive glucose stimulations. It, therefore, appears that the response pattern is a characteristic of the individual beta-cell. We have now investigated if a cell-specific [Ca2+](i) response is a general phenomenon in rodent beta-cells, and if it can be observed when cells are functionally coupled. With the use of the fura-2 technique, we have studied the 'early [Ca2+](i) response' in single dispersed beta-cells, in beta-cell clusters of different size and in intact islets from the ob/ob mouse during repeated glucose stimulation (20 mM). beta-Cells from lean mouse and rat, and intact islets from lean mouse were also investigated. Significant correlations between the first and second stimulation were found for the parameters lag-time for Ca2+ rise (calculated as the time from start of stimulation of the cell until the first value above an extrapolated baseline), nadir of initial lowering (difference between the baseline and lowest [Ca2+](i) value), and peak height (difference between baseline and the highest [Ca2+](i) value of the first calcium peak) in single dispersed beta-cells, in 'single beta-cell within a small cluster', in clusters of medium and large size, and in single dispersed beta-cells from lean mouse and rat. The lag-times for Ca2+ rise and peak heights were correlated within the pairs of stimulation also in intact ob/ob islets. In summary, despite a large heterogeneity of the 'early [Ca2+](i) response' among individual cells, the lag-time for [Ca2+](i) rise, the nadir of initial lowering and the height of the first peak response can be identified as cell-specific markers in beta-cells. (C) 2003 Elsevier Science Ltd. All rights reserved.