Effect of a new hypoglycaemic agent (HB 699) on the in vivo secretion of pancreatic hormones in the dog.
The effects of HB 699, a non-sulphonyl urea acyl-amino-alcyl benzoic acid derivative, were studied in unanesthetized 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 dose-dependent manner. The effects of HB 699 (40 mg/kg) on pancreatic hormone secretion were compared to those of tolbutamide give 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.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000097:blood*; D013004:Somatostatin / Q000097:blood*
D001549:Benzamides; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; C030516:meglitinide; D005934:Glucagon