Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in beta-cells from hyperglycemic mice.
We recently reported that the timing and magnitude of the nutrient-induced Ca(2+) response are specific and reproducible for each isolated beta-cell. We have now used tolbutamide and arginine to test if the cell specificity exists also for the response to non-nutrient stimulation of beta-cells and if so, whether it is disturbed in beta-cells from hyperglycemic ob/ob and db/db mice. Zn(2+) outflow measurements were used to study the correlation between Ca(2+) response and insulin secretion in individual beta-cells. Tolbutamide and arginine induced cell-specific Ca(2+) responses in lean mouse beta-cells both with regard to lag times for [Ca(2+)](i) rise and peak [Ca(2+)](i) heights. beta-Cells within intact islets also showed cell-specific timing of their Ca(2+) responses to tolbutamide. However, in tolbutamide- and arginine-stimulated single beta-cells from ob/ob and db/db mice only the magnitude of Ca(2+) response was cell-specific, not the timing. The lag time of tolbutamide-induced insulin secretion was cell-specific in lean mouse beta-cells but not in ob/ob mouse cells. Therefore, cell specificity seems to be a robust mechanism, and probably important for an adequate beta-cell function. The loss of temporal cell specificity for the response to tolbutamide in single beta-cells from hyperglycemic mice may be a sign of K(ATP)- or voltage-dependent calcium channel dysfunction.
Gustavsson
Natalia
N
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå S-901 87, Sweden. natalia.gustavsson@histocel.umu.se
Larsson-Nyrén
Gerd
G
Lindström
Per
P
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006943:Hyperglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D014044:Tolbutamide / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D014044:Tolbutamide; D002118:Calcium