Glimepiride Administered in Chow Reversibly Impairs Glucose Tolerance in Mice

Figure 1

Glimepiride treatment impairs glucose tolerance in C57Bl/6J mice. Wild-type C57Bl/6J mice were treated for two weeks with glimepiride (1 or 8 mg/kg/day) or control chow, after which a glucose tolerance test (GTT) was performed. Blood glucose was measured after a 6-hour fast (time = 0). The mice were then injected with glucose (2 mg/g body weight), and the blood glucose was measured over the next 2 hours. Mice treated with 8 mg/kg/day glimepiride had significantly elevated fasting blood glucose and higher blood glucose at and 120 minutes (a) (). Closed circles = control group; open circles = 1 mg/kg/day; inverted triangles = 8 mg/kg/day glimepiride. The area under the curve was also calculated for the GTT time course as a representation of glucose tolerance. Mice treated with 8 mg/kg/day glimepiride had significantly impaired glucose tolerance (bigger area under the curve) than control animals (b) (). Treatment with 1 mg/kg/day glimepiride trended toward impaired glucose tolerance, though this did not reach significance (). /group. Circulating insulin (c) and glucagon (d) levels were measured after glimepiride treatment (8 mg/kg/day; /control, /glimepiride). Serum insulin was decreased by approximately 50% in mice treated with glimepiride (). Unlike insulin, serum glucagon was unaffected by glimepiride treatment. Gluconeogenesis was assessed using a pyruvate tolerance test. Even after an overnight fast, glimepiride-treated mice had elevated fasting blood glucose (e) (). However, there was no difference in blood glucose in any of the other time points, or in the area under the curve (f). /control; /glimepiride. Closed circles = control diet; open circles = glimepiride group.

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