The mechanism of action of sulphonylureas is not completely understood. In the present study we evaluated the effects of
gliquidone, a second-generation compound, on several metabolic parameters in 22 patients with untreated newly-diagnosed type II (
noninsulin-dependent) diabetes mellitus. After either 1 or 6 months of treatment with
gliquidone plus isocaloric diet we observed: 1) a significant decrease in fasting plasma
glucose and glycemic profile after oral
glucose load; 2) unchanged fasting and postglucose plasma
insulin levels; 3) no change in fasting
C-peptide levels but a significant increase in
C-peptide concentrations after
glucose challenge; 4) a significant increase in
glucose disappearance rate from plasma following iv
insulin injection; 5) an increase in the
insulin-induced reduction of plasma levels of
free-fatty acids; 6) no change in plasma
C-peptide levels following iv
insulin injection; 7) a significant increase in specific
insulin binding to monocytes. After 6 but not 1 month of
gliquidone therapy we also found an increase in the activity of
hexokinase in circulating mononuclear leukocytes. These results suggest that the
hypoglycemic effect of
gliquidone occurs through either an increased beta cell response to
glucose stimulus or an enhanced
insulin sensitivity. The latter effect seems to depend on both receptor and postreceptor mechanisms.