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Loperamide increases glucose ultilization in streptozotocin‐induced diabetic rats
Author(s) -
Tzeng TF,
Liu IM,
Lai TY,
Tsai CC,
Chang WC,
Cheng JT
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03903.x
Subject(s) - streptozotocin , loperamide , diabetes mellitus , medicine , endocrinology , traditional medicine , pharmacology , chemistry , diarrhea
Summary 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 µg/kg) to activate µ‐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 µg/kg) to STZ‐diabetic rats over 3 days. Moreover, similar treatment with loperamide (17.6 µg/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 µ‐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.