Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats

Control and streptozotocin-induced diabetic rats, as well as GK rats, received a single oral administration of either nateglinide (50 microg/g body wt.) or glibenclamide (1.0 microg/g body wt.). The plasma D-glucose and insulin concentrations, as well as the content of plasma, liver and pancreas in either nateglinide or glibenclamide were measured 60 min or 24 hours after the administration of these antidiabetic agents. At the 60th min, the plasma, hepatic and pancreatic content of nateglinide largely exceeded that of glibenclamide. At the 24th hour, however, the plasma concentration, as well as liver and pancreas content, of nateglinide became negligible, whilst that of glibenclamide exceeded the values recorded at the 60th min. A comparable pattern characterized the insulinotropic action and hypoglycemic effect of these two antidiabetic agents. This study thus emphasizes the vastly different pharmacodynamics of nateglinide and glibenclamide in both control and diabetic rats.