Cell specificity of the cytoplasmic Ca super(2+) response to tolbutamide is impaired in {szligbeta}-cells from hyperglycemic mice

We recently reported that the timing and magnitude of the nutrient-induced Ca super(2+) response are specific and reproducible for each isolated {szligbeta}-cell. We have now used tolbutamide and arginine to test if the cell specificity exists also for the response to non-nutrient stimulation of {szligbeta}-cells and if so, whether it is disturbed in {szligbeta}-cells from hyperglycemic ob/ob and db/db mice. Zn super(2+) outflow measurements were used to study the correlation between Ca super(2+) response and insulin secretion in individual {szligbeta}-cells. Tolbutamide and arginine induced cell-specific Ca super(2+) responses in lean mouse {szligbeta}-cells both with regard to lag times for [Ca super(2+)] sub(i) rise and peak [Ca super(2+)] sub(i) heights. {szligbeta}-Cells within intact islets also showed cell-specific timing of their Ca super(2+) responses to tolbutamide. However, in tolbutamide- and arginine-stimulated single {szligbeta}-cells from ob/ob and db/db mice only the magnitude of Ca super(2+) response was cell-specific, not the timing. The lag time of tolbutamide-induced insulin secretion was cell-specific in lean mouse {szligbeta}-cells but not in ob/ob mouse cells. Therefore, cell specificity seems to be a robust mechanism, and probably important for an adequate {szligbeta}-cell function. The loss of temporal cell specificity for the response to tolbutamide in single {szligbeta}-cells from hyperglycemic mice may be a sign of K sub(ATP)- or voltage-dependent calcium channel dysfunction.