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+.
ACKNOWLEDGMENTS Hoechst A. G. (Frankfurt/Main, Federal Republic of Germany) kindly donated tolbutamide, compound 17710, and [125I]insulin. The author is indebted to Inger Rönnberg, Lilian Forsberg, and Kristina Stensjö for technical assistance.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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