ANTAZOLINE INCREASES INSULIN-SECRETION AND IMPROVES GLUCOSE-TOLERANCEIN RATS AND DOGS

In vivo effects of an imidazoline devoid of alpha(2)-adrenoceptor anta gonistic properties, antazoline, on insulin secretion and glycemia wer e investigated both in fasted rats and dogs. In both species, antazoli ne (1.5 mg/kg i.v.) transiently increased insulinemia without affectin g basal plasma glucose levels. In contrast, during an i.v. glucose tol erance test, antazoline markedly potentiated insulin release and thus increased the glucose disappearance rate. In rats, during an oral gluc ose tolerance test, the intragastric administration of antazoline (1.5 mg/kg) clearly enhanced insulin secretion and reduced hyperglycemia. In dogs provided with a venous pancreatico-duodenal bypass, antazoline (0.5 mg/kg i.v.) induced an immediate and transient increase in Insul in and somatostatin but not in glucagon pancreaticoduodenal outputs. I n conclusion, intravenously and orally administered, the imidazoline a ntazoline is able to stimulate insulin secretion in vivo and improve g lucose tolerance. The imidazoline compounds could therefore have a pot ential therapeutic relevance as new antihyperglycemic insulinotropic a gents.