Glimepiride Administered in Chow Reversibly Impairs Glucose Tolerance in Mice

Figure 6

Glimepiride impairs glucose tolerance and suppresses insulin secretion in Grn^−/− mice. Grn^−/− mice were treated with glimepiride (0, 1, or 8 mg/kg/day) for two weeks, after which a glucose tolerance test was performed. Both doses of glimepiride led to an increase in fasting blood glucose in these mice (a) (/control,  mg/kg/day,  mg/kg/day). Closed circles = control; open circles = 1 mg/kg/day glimepiride; inverted triangles = 8 mg/kg/day glimepiride. In addition, both doses increased blood glucose during at least part of the GTT, leading to an increase in the area under the curve (b). Serum insulin was lower in Grn^−/−mice than wild-type (c) (/group). Glimepiride (8 mg/kg/day) treatment significantly reduced circulating insulin in wild-type mice, but there was no change in Grn^−/− mice. Note that any samples that were below the detection limit for the insulin ELISA were set to 0 and included in the group mean. Glucagon was unaffected by both genotype and glimepiride treatment (d) (/group). Black bars = C57Bl/6J wild-type; white bars = Grn^−/− mice. We tested nicorandil (15 mg/kg/day), another compound that targets sulfonylurea receptors, but is specific for SUR2. Unlike glimepiride, nicorandil treatment had no effect on fasting blood glucose (e) or glucose tolerance (f) (/control, /glimepiride, /nicorandil). . Closed circles = control; open circles = glimepiride (8 mg/kg/day); inverted triangles = nicorandil.

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