Does fluoxetine administration influence insulin resistance in 90% pancreatectomized rats?

This study evaluates the effect of fluoxetine (FXTN) on insulin resistance and glucose uptake by various tissues in 90% pancreatectomized (Px) and sham-operated (Sham) rats. Both the Px and Sham rats were divided into 2 groups: 1 group was given FXTN (5 mg/kg) for 8 weeks, and the other group was given a placebo. Whole body glucose disposal rates were measured using euglycemic hyperinsulinemic (EH) clamps while the rats were in an awake, unstressed, and fasting state. On the following day, all rats were intravenously injected with [1-(14)C]2-deoxyglucose solution and killed 45 minutes later. The body weight of the FXTN group was lower than that of the placebo group in the Sham and Px rats during the first 2 weeks (P <.05), but there was no difference in body weight between these groups after the third week. Evidently, FXTN did not alter serum glucose levels in the Sham and Px rats. Basal serum insulin levels at EH clamp were significantly lower in the FXTN group than the placebo group in Sham rats. Whole body glucose disposal rates increased with FXTN administration in Sham rats (44.8 +/- 3.4 v 36.4 +/- 2.9 mg/kg/min) and in Px rats (33.9 +/- 3.6 v 25.5 +/- 4.1 mg/kg/min) compared with placebo administration. The glycogen content of the soleus muscle tissue was higher in the FXTN group than in the placebo group of Sham and Px rats. The dose percentage of [1-(14)C]2-deoxyglucose uptake by soleus muscle tissue was higher in the FXTN group than in the placebo group of Sham and Px rats. In conclusion, (1) FXTN improves insulin sensitivity beyond the effect mediated through weight loss and (2) the effect of FXTN on insulin sensitivity may be achieved by increased glucose uptake and glycogen synthesis in the soleus muscle tissue.