EFFECTS OF S-4-ISOPROPYLCYCLOHEXYL)-CARBONYL]-D-PHENYLALANINE (A-4166) ON INSULIN AND GLUCAGON-SECRETION IN ISOLATED-PERFUSED RAT PANCREAS

s-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) has a stru cture which differs from those of other known blood glucose-lowering a gents including sulfonylureas. It has been shown that oral administrat ion of A-4166 exerts blood glucose-lowering effects in animal in vivo studies. In the present study, we investigated the effects of A-4166 o n insulin and glucagon secretion at several glucose concentrations usi ng isolated perfused rat pancreas preparations. Both 3.0 and 30 mu mol /l A-4166 signigicantly stimulated insulin secretion as compared with basal levels at glucose concentrations of 8.0 and 11.0 mmol (p<0.01 an d p<0.05, respectively). In contrast, glucagon secretion was not affec ted by administration of A-4166 up to 30 mu mol/l at these glucose con centrations. At a glucose concentration of 5.6 mmol/l, neither 0.3 nor 3.0 mu mol/l A-4166 produced significant changes in insulin and gluca gon secretion. However, A-4166 at 30 mu mol/l significantly stimulated insulin secretion and inhibited glucagon secretion as compared with b asal levels (p<0.01 and p<0.01, respectively). We conclude that A-4166 at 3.0 and 30 mu mol/l directly stimulates insulin secretion but has little effect on glucagon secretion in isolated perfused rat pancreas at glucose concentrations of 8.0 and 11.0 mmol/l. these results, taken together with previously published data, suggest that oral administra tion of A-4166 could be a useful strategy for stimulating endogenous i nsulin secretion in non-insulin-dependent diabetic patients.