Temporal effect of varying doses of clonidine on the fasting blood glucose levels of sprague dawley rats

Abstract

Background Primarily used as a centrally-acting anti-hypertensive drug, clonidine has also been shown to affect blood glucose determinants by acting on peripheral α-2 adrenoreceptors. However, the studies which investigate the effect of clonidine on blood glucose levels yielded conflicting results depending on conditions applied. Methods Thirty-five (35) adult male Sprague-Dawley rats weighing 140-330 grams were randomly and equally assigned to five treatment groups of varying clonidine doses: 1, 2, 4, 7μg/kg and 0.9% NaCl (control). The doses were administered intra-peritoneally after fasting the rats for 18 hours. Whole blood samples (at least 1 μl) were obtained via tail pricking/tail lancing and measured for glucose levels using a commercially available glucometer (One-touch Ultra ®) 1 hour before injection to get baseline blood glucose levels and every hour for 8 hours after injection to measure changes in blood glucose levels. The rats remained fasted until after the 8-hour monitoring period. Data were analyzed using t-test, Analysis of Variance(ANOVA) and Tukey LSD at 95% confidence interval (α=0.05). Area under the curve (AUC) reflecting the cumulative blood glucose level within the first 8-hour monitoring period for each dosage was computed. Results Significant differences among fasting blood glucose levels of 2, 4, 7 μg/kg and control groups were observed at the 1st to 4th hour after injection, with the treatment groups having higher glucose levels than the control group. No significant difference was observed between the 1 μg/kg group and control group. At the 5th hour onwards, no significant difference was noted among treatment means. Cumulative dose effect of clonidine (AUC) showed a significant rise in glucose at 4 and 7 μg/kg with apparent saturation at 4 μg/kg when plotted in a dose-response curve. Conclusions Intra-peritoneal administration of clonidine significantly increases blood glucose levels when administered at 2, 4 and 7 μg/kg with peak effect at 1st to 3rd hour post injection and no significant difference starting at 5th hour post-injection onwards. Optimal dosage is found to be at 4 μg/kg.