Enhancement of insulin release and islet cell calcium content by an acyl-amino-alkyl benzoic acid derivative, HB 699

HB 699, a hypoglycaemic agent which lacks the structural requirements regarded as essential for the insulin releasing action of the sulfonamide group, was studied in isolated rat islets and compared with tolbutamide. In the presence of 8.3 mM glucose for long exposure (24 h) both substances induced an increase of insulin release without altering the islet insulin content. After preloading of the islets to isotopic equilibrium with 45Ca++ (24 h), HB 699 and tolbutamide induced a significant increase in total exchangeable calcium content parallelled by an increase in insulin release. Both effects could be suppressed by verapamil, a blocker of voltage-sensitive Ca++ channels. These results indicate that HB 699, like tolbutamide, stimulates insulin release by increasing Ca++ uptake by the B cells.