Plasma glucose-lowering effect of tramadol in streptozotocin-induced diabetic rats

Juei Tang Cheng, I. Min Liu, Tzong Cherng Chi, Thing Fong Tzeng, Feng Hwa Lu, Chih Jen Chang

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101 Citations (Scopus)


The effect of tramadol on the plasma glucose level of streptozotocin (STZ)-induced diabetic rats was investigated. A dose-dependent lowering of plasma glucose was seen in the fasting STZ-induced diabetic rats 30 min after intravenous injection of tramadol. This effect of tramadol was abolished by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid μ-receptors. However, response to tramadol was not changed in STZ-induced diabetic rats receiving p-chlorophenylalanine at a dose sufficient to deplete endogenous 5-hydroxytrptamine (5-HT). Therefore, mediation of 5-HT in this action of tramadol is ruled out. In isolated soleus muscle, tramadol enhanced the uptake of radioactive glucose in a concentration-dependent manner. The stimulatory effects of tramadol on glycogen synthesis were also seen in hepatocytes isolated from STZ-induced diabetic rats. The blockade of these actions by naloxone and naloxonazine indicated the mediation of opioid μ-receptors. The mRNA and protein levels of the subtype 4 form of glucose transporter in soleus muscle were increased after repeated treatments for 4 days with tramadol in STZ-induced diabetic rats. Moreover, similar repeated treatments with tramadol reversed the elevated mRNA and protein levels of phosphoenolpyruvate carboxykinase in the liver of STZ-induced diabetic rats. These results suggest that activation of opioid μ-receptors by tramadol can increase the utilization of glucose and/or decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.

Original languageEnglish
Pages (from-to)2815-2821
Number of pages7
Issue number12
Publication statusPublished - 2001 Dec

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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