Differences in Insulin Secretion in Portal Blood after Administration of Glimepiride and Glibenclamide : A Study in OLETF Rats

Aims:To clarify differences in insulin-secretagogue and antihyperglycemic properties between glimepiride and glibenclamide. Methods:Catheters were inserted into the portal veins of 12-week-old,obese,spontaneously type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats and left in place.After 17-hour fasting, the rats were given either 1 mg/kg of glibenclamide,1 mg/kg of glimepiride,or 0.5% methylcellulose(control),and then immediately given oral glucose 1 g/kg. Results:Portal insulin levels increased after glucose loading and began to decrease 60 minutes after glucose loading in the glimepiride group,but those in the glibenclamide group were significantly higher than those in the glimepiride group and continued to increase wel after 60 minutes after glucose loading.The area under the curve for insulin did not differ between the glibenclamide group(1,259±674 ng min/dL)and the glimepiride group(1,068±388 ng min/dL)for 0 to 60 minutes but was significantly lower in the glimepiride group(1,901±928 ng min/dL)than in the glibenclamide group(3,392±1,047 ng min/dL)for 60 to 270 minutes.Glucose levels in peripheral blood after glucose loading were significantly lower than control in the glibenclamide group after 120 minutes and in the glimepiride group after 60 minutes,but the area under the curve for glucose did not differ significantly between the glibenclamide group(29,213±6,449 mg min/dL)and glimepiride group(24,524±3,618 mg min/dL). Conclusions:Glimepiride has a faster onset of action but otherwise has antihyperglycemic properties similar to those of glibenclamide.In contrast,glimepiride is a weaker,shorter-acting insulin secretagogue than is glibenclamide. (Jikeikai Med J 2003;50:173-7)