The acyl-amino-alkyl benzoic acid residue and the sulfonylurea containing residue of glibenclamide affect different aspects of beta-cell function.

HB 699 is a non-sulfonylurea acyl-amino-alkyl benzoic acid derivative, corresponding to a major part of the glibenclamide molecule. Basal insulin release (3 mmol/l glucose) as well as glucose-induced release (10 mmol/l glucose) were stimulated by 25 mumol/l and 200 mumol/l HB 699. HB 699 (200 mumol/l) had no effect on the osmotic swelling induced by hypoosmolarity (180 mosm/l). The results indicate that the glibenclamide-induced insulin release can be resolved in a "high-affinity" component, which correlates with increased osmotic resistance in the beta-cells and a "low-affinity" component not associated with increased osmotic resistance. It is suggested that the latter component may be due to the part of the glibenclamide molecule that corresponds to HB 699.