EFFECTS OF BENZOIC-ACID AND ITS ANALOGS ON INSULIN AND GLUCAGON-SECRETION IN SHEEP

The effects of benzoic acid and its analogues on insulin and glucagon secretion were investigated in conscious sheep. Intravenous injections of benzoic acid increased plasma insulin and glucagon concentrations in a dose-dependent manner between 39-1250 mu mol/kg, with ED(50)s for increasing both hormones of about 625 mu mol/kg. Various derivatives of benzoic acid (625 mu mol/kg) were administered and structure-activi ty relationships were examined. A single carboxylic group was essentia l for stimulating insulin and glucagon secretion, since both hormone r esponses were abolished with compounds in which the carboxylic group w as replaced by sulfonic or phosphoric groups, or in which another carb oxylic element was introduced (phthalic acids). Most of the compounds which introduced other elements (amino and hydroxy groups, and halogen s) onto the benzene ring had an altered stimulating activity. Thus the pancreatic endocrine system can recognize the chemical structure of b enzoic acid and its derivatives in detail and induce insulin and gluca gon secretion in sheep.