Abstract

Tolbutamide and glucose were compared with regard to their actions on ⁴⁵Ca fluxes in pancreatic islets microdissected from ob/ob mice. In contrast to an analogue lacking effects on insulin release, tolbutamide stimulated the intracellular net uptake of ⁴⁵Ca as well as the efflux of the isotope. The magnitude of both effects equaled those produced by 20 mM glucose. The tolbutamide stimulation of ⁴⁵Ca efflux was more rapidly established than that with glucose; combination of glucose and tolbutamide did not increase the efflux more than with either alone. Comparisons of the ⁴⁵Ca efflux from islets loaded in the presence of tolbutamide or glucose suggested that these compounds had different effects of the intracellular distribution of the incorporated ⁴⁵Ca. The action of tolbutamide diverged from that of glucose also in not inhibiting the ⁴⁵Ca efflux during perifusion with Ca²⁺-deficient medium. It is likely that the tolbutamide effect on the β-cell handling of ⁴⁵Ca is essentially due to opening of potential-dependent channels with resulting increase in the entry of Ca²⁺.