Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in β-cells from hyperglycemic mice

Abstract

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