Loperamide increases glucose ultilization in streptozotocin-induced diabetic rats.
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 microg/kg) to activate mu-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 microg/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 mu-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.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy*; D051275:Glucose Transporter Type 4; D008139:Loperamide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D008139:Loperamide; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases