Activation of opioid mu-receptor by loperamide to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigated the effect of loperamide, a selective agonist of opioid mu-receptor, on the plasma glucose in diabetic rats induced by an intravenous injection of streptozotocin (STZ; 60 mg/kg). Intravenous injection of loperamide induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats at 30 min later, but did not modify the plasma glucose level in Wistar rats. Plasma glucose lowering effect of loperamide was abolished by the pretreatment with naloxone or naloxonazine at the dose sufficient to block opioid mu-receptor. In isolated skeletal muscle, loperamide enhanced the glucose uptake into soleus muscles in a concentration-dependent manner. Blockade of this action by naloxonazine indicated the mediation of opioid mu-receptor. These results suggest that an activation of opioid mu-receptor by loperamide can increase the utilization of glucose in peripheral tissue to lower the plasma glucose in STZ-diabetic rats.