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Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå S-901 87, Sweden

(Requests for offprints should be addressed to N Gustavsson; Email: natalia.gustavsson{at}histocel.umu.se)

We recently reported that the timing and magnitude of the nutrient-induced Ca²⁺ response are specific and reproducible for each isolated ß-cell. We have now used tolbutamide and arginine to test if the cell specificity exists also for the response to non-nutrient stimulation of ß-cells and if so, whether it is disturbed in ß-cells from hyperglycemic ob/ob and db/db mice. Zn²⁺ outflow measurements were used to study the correlation between Ca²⁺ response and insulin secretion in individual ß-cells. Tolbutamide and arginine induced cell-specific Ca²⁺ responses in lean mouse ß-cells both with regard to lag times for [Ca²⁺]_i rise and peak [Ca²⁺]_i heights. ß-Cells within intact islets also showed cell-specific timing of their Ca²⁺ responses to tolbutamide. However, in tolbutamide- and arginine-stimulated single ß-cells from ob/ob and db/db mice only the magnitude of Ca²⁺ response was cell-specific, not the timing. The lag time of tolbutamide-induced insulin secretion was cell-specific in lean mouse ß-cells but not in ob/ob mouse cells. Therefore, cell specificity seems to be a robust mechanism, and probably important for an adequate ß-cell function. The loss of temporal cell specificity for the response to tolbutamide in single ß-cells from hyperglycemic mice may be a sign of K_ATP- or voltage-dependent calcium channel dysfunction.