Effect of a new hypoglycaemic agent (HB 699) on the in vivo secretion of pancreatic hormones in the dog

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Abstract
The effects of HB 699, a non-sulphonyl urea acyl-amino-alcyl benzoic acid derivative, were studied in unanaesthetized dogs. Changes in blood glucose and plasma insulin, glucagon, pancreatic polypeptide and somatostatin were measured after a single intravenous injection. HB 699 caused hypoglycaemia and stimulated insulin secretion in a dosedependent manner. The effects of HB 699 (40 mg/ kg) on pancreatic hormone secretion were compared to those of tolbutamide given at a dose (12 mg/kg) which induced a similar maximal hypoglycaemia. Both drugs caused a similar increase in insulin release (180±32% for tolbutamide and 240±41% for HB 699) lasting for approximately 1 hour. Despite hypoglycaemia, plasma glucagon concentrations were unaltered by either substance. HB 699 caused a marked increase in the secretion of pancreatic polypeptide (220±60% at 30 min) for up to 2 hours, whereas tolbutamide caused no significant change in plasma pancreatic polypeptide levels. In contrast, while tolbutamide caused a significant (45±12%) but short-lived increase in plasma somatostatin concentrations, HB 699 had no significant effect.