The influence of chlorpropamide pre-treatment on insulin and growth hormone release after arginine.

THE hypoglycaemic effect of the sulphonylurea family of drugs was long suspected to be secondary to endogenous insulin release from the pancreatic islets. This was confirmed by Yalow et al. (1960) who showed a rise in peripheral plasma concentration of insulin after tolbutamide administration to normal subjects. More recently, Coore & Randle (1964) showed that, when isolated segments of rabbit pancreas were incubated in the presence of tolbutamide, there was additional release of insulin into the medium. Further evidence that the sulphonylurea drugs increase pancreatic islet-cell activity emerged from the thorough studies of Fajans et al. (1963) and Floyd et al. (1963). These authors showed that, whereas the amino acid, L-leucine, induced only a modest rise in peripheral plasma insulin concentration in normal subjects, the response was dramatically enhanced by pre-treatment of these subjects with chlorpropamide. Floyd et al. (1966) have since shown that infusion of a number of amino acids, including L-arginine, is followed by a rise in peripheral plasma insulin levels. We have confirmed that arginine infusion initiates a rise in plasma insulin concentration. There is, in addition, a rise in plasma HGH concentration after arginine, a response which is quantitatively greater in the female than in the male (Merimee, Lillicrap & Rabinowitz, 1965; Merimee, Burgess & Rabinowitz, 1966). In the light of the considerable influence of chlorpropamide on leucine-initiated insulin release, we were led to explore the effect of this sulphonylurea on arginine-initiated hormonal release. We chose a dosage schedule of arginine monochloride which usually produces only a modest increment in plasma insulin in control subjects. Plasma glucose, insulin and HGH responses following a standard load of L-arginine to seven normal males before and after chlorpropamide pre-treatment form the basis of this report.