Glimepiride Administered in Chow Reversibly Impairs Glucose Tolerance in Mice

Figure 4

C57Bl/6N mice have decreased insulin, but normal insulin tolerance in response to glimepiride (8 mg/kg/day) treatment. Mice were fasted for 6 hours prior to the start of the GTT. There was no difference in nonfasting blood glucose between control and glimepiride-treated mice (a). Control-fed mice maintain a constant blood glucose levels during this fast. Glimepiride-fed mice, on the other hand, have increased blood glucose after the 6-hour fast. We also tested insulin levels before and after fasting. Even in nonfasting animals, glimepiride treatment decreases circulating insulin levels (b). Insulin decreases in control-fed mice during the fasting period, but does not change in glimepiride-fed animals. Administration of a glucose bolus stimulated insulin secretion in control-fed animals, but not in glimepiride-fed animals. Black bars = control group; white bars = glimepiride group (8 mg/kg/day). In order to measure insulin sensitivity, we performed an insulin tolerance test. Glimepiride-treated mice are as sensitive to insulin as control-treated mice (c). In fact, glimepiride-treated mice have lower blood glucose 15 minutes after insulin injection. Closed circles = control group; open circles = glimepiride group. Liver glycogen levels were not significantly different in glimepiride-treated mice, though there was a trend towards an increase -value of < 0.2 (d). /group: .

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