The effects of glibenclamide on rat islet radioactive nucleotide efflux, ATP contents and respiratory rates.

In order to assess the effects of sulphonylurea on islet function, changes in radioactive nucleotide efflux, ATP contents and oxygen uptake of low or high glucose cultured rat islets in response to glibenclamide were determined. It was observed that: (1) low glucose cultured islets displayed a prompt increase in radioactive efflux in response to glibenclamide when perfused in the presence of 1.7, 5.6 and 11.1 mM glucose. The response was most prominent in the presence of 5.6 mM glucose. (2) High glucose cultured islet did not respond to glibenclamide with increased radioactive efflux in the presence of 11.1 mM glucose, in contrast to the effects in the presence of 1.7 or 5.6 mM glucose. The sulphonylurea-induced changes could be delayed by adding glibenclamide in parallel with a decrease in glucose from 20 to 1.7 mM. (3) No effects of glibenclamide on radioactive nucleotide efflux from either low or high glucose cultured islets could be observed in the absence of extracellular Ca2+. (4) Glibenclamide decreased the islet ATP content of low glucose cultured islets in the presence of 5.6 mM glucose. On the contrary, the ATP content of high glucose cultured islets was increased by glibenclamide with 1.7 mM glucose present. (5) Islet respiration was increased by adding glucose in both high or low glucose cultured islets, although respiration in the presence of both 5.6 and 11.1 mM glucose was higher in high glucose cultured islets. (6) The addition of glibenclamide decreased oxygen uptake of low glucose cultured islets in the presence of 5.6 and 11.1 mM glucose and that of high glucose cultured islets at all glucose concentrations tested (1.7, 5.6 and 11.1 mM). It is concluded that glibenclamide-induced changes in radioactive nucleotide efflux may reflect metabolic and ionic changes of importance to islet functions.