Clin Exp Pharmacol Physiol. 2003 Oct; 30(10): 734-738.

Loperamide increases glucose ultilization in streptozotocin-induced diabetic rats.

Tzeng T, Liu I, Lai T, Tsai C, Chang W, Cheng J.

Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Shien, Department of Traditional Medicine, School of Post-Baccalaureate Chinese Medicine and Department of Sports Medicine, China Medical College, Taichung City and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.

1. Loperamide has an ability to lower the plasma glucose concentration in streptozotocin (STZ)-induced diabetic rats. In the present study, we investigated the molecular mechanisms by which loperamide regulates plasma glucose concentrations in the absence of insulin. 2. Loperamide, at a dose sufficient (17.6 micro g/kg) to activate micro -opioid receptors, significantly decreased plasma glucose levels in STZ-diabetic rats. The mRNA and protein levels of glucose transporter 4 (GLUT-4) in soleus muscle, detected by northern and western blotting, respectively, were increased after repeated intravenous administration of loperamide (17.6 micro g/kg) to STZ-diabetic rats over 3 days. Moreover, similar treatment with loperamide (17.6 micro g/kg) for 3 days reversed the elevated mRNA and protein levels of phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats to near the levels seen in normal rats. 3. These results suggest that activation of micro -opioid receptors by loperamide can increase glucose utilization in peripheral tissues and/or reverse the higher gene expression of PEPCK to inhibit hepatic gluconeogenesis, thereby lower plasma glucose in diabetic rats lacking insulin.