Insulinotropic Effect and Possible Mode of Action of a New Potent Sulfonylurea (BS-4231)

BS-4231, a new sulfonylurea, stimulates insulin secretion by incubated pieces of rat pancreatic tissue. The minimal effective dose is between 3 and 30 mμg/ml. The insulinotropic effect of this agent is transient. It is more marked at intermediate (1.0 and 1.5 mg/ml) than either at high glucose concentrations (3.0 mg/ml) or in the absence of glucose. Experimental data obtained with various inhibitors of insulin secretion suggest that (i) epinephrine suppresses the stimulant action of BS-4231, as well as that of glucose; (ii) mannoheptulose modulates the insulinotropic action of BS-4231 indirectly by altering the effect of extracellular glucose; and (iii) diazoxide faiis to exert any effect upon insulin secretion in the presence of BS-4231. On the basis of these results, it is suggested that BS-4231 might accelerate within the beta-cell some step of glucose metabolism, which is rate-limiting when the insulin secretory process is not fully stimulated by extracellular glucose.