Effect of linogliride on hormone release from perfused rat pancreas. Fuel dependence and desensitization by tolbutamide.

We examined the effect of the hypoglycemic drug linogliride on hormone release from the in vitro perfused rat pancreas. Linogliride stimulated insulin release in the absence of glucose either in the presence or absence of a physiological mixture of amino acids. In addition, linogliride inhibited amino acid-induced glucagon release. Half-maximal effects of linogliride on insulin and glucagon release were achieved at concentrations as low as 26 and 3 microM, respectively. The effects of linogliride on hormone release largely resembled those of tolbutamide. In the absence of amino acids, the stimulation of insulin release by linogliride or tolbutamide was transient. When the pancreas had been preperfused for 20 min with tolbutamide, linogliride no longer had an effect on hormone release. Likewise, tolbutamide remained without effect in pancreases preperfused with linogliride. These data suggest that linogliride and tolbutamide may have a similar mechanism of action.