Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication

Abstract Background Artesunate is an antimalarial drug that affects glucose homeostasis but the mechanism of its glucose-modulating effect is not fully understood especially with gender implication, which is the information this study sought to provide. Methods Twenty-five (25) male and 25 female rats were separately and blindly allocated into five identical groups (n = 5/group). Group I (control) received 0.2 ml/kg distilled water. Groups II and III both received 2.90 mg/kg artesunate on day one, but 1.45 mg/kg from day two till day five and day fifteen respectively. Groups IV and V both received 8.70 mg/kg artesunate on day one, but 4.35 mg/kg artesunate from day two till day five and day fifteen respectively. Results In male rats, the blood glucose was reduced by low and high doses of artesunate at 5 days but increased by high dose at 15 days. Glucose was reduced in female rats but unchanged in male rats by low dose artesunate at 15 days. Artesunate increased glycogen concentration at short duration which normalised at long duration in both genders. Artesunate increased G6P concentration only in male rats at 15 days but reduced G6Pase activity in male and female rats (except in those that received low and high doses of artesunate for 15 days). Artesunate increased insulin only in male rats treated with low dose artesunate for 5 days. Artesunate increased cortisol concentration in male but reduced it in female rats. Artesunate decreased glucagon concentration except in female rats treated with high dose for 5 days. Artesunate increased oestrogen concentration in male rats that received low dose artesunate for 5 days but reduced it in female rats that received high dose for 15 days. Except in male rats that received high dose of artesunate for 15 days where testosterone was increased, artesunate did not affect testosterone concentration in all other male and female groups Conclusions The present study suggests that artesunate causes reduction in plasma glucose by reducing plasma glucagon concentrations and inhibiting liver glycogenolysis via inhibition of G6Pase activity in both sexes. In addition, increase in plasma insulin concentration contributed to the reduction in blood glucose caused by artesunate in male but not female rats; and artesunate-induced increase in G6P, a substrate for G6PD, could enhance NADPH generation and antioxidant enzyme activation in male rats.