Effect of some opioids on plasma glucose and liver glycogen in STZ-induced diabetic rats

ABSTRACT

Opioid analgesics are used widely to control various types of pain. Several studies reported that opioid analgesics may produce lowering plasma glucose. The present work aims to investigate the effect of both tramadol and fentanyl on the plasma glucose and liver glycogen of streptozotocin [STZ] induced diabetic rats and declares the possible mechanism of this effect. IV administration of either tramadol or fentanyl for 4 successive days in STZ-induced diabetic rats produced significant reduction in fasting and random plasma glucose in comparison with non-treated STZ-induced diabetic rats. IV Naloxone [mu opioid [MOP] receptor blocker] 30 min. before administration of either tramadol or fentanyl blocked the effect of both tramadol and fentanyl on fasting and random plasma glucose. IV injection of both tramadol and fentanyl in STZ-induced diabetic rats for 4 successive days, produced significant recovery [increase] of glycogen content of the liver in diabetic rats compared with diabetic non-treated group. This effect was also blocked by IV naloxone administration 30 min before administration of either tramadol or fentanyl. The histochemical examination of PAS stained sections of the liver, prepared from rats used during this work, confirmed the results obtained by chemical detection of glycogen content of the liver homogenate. I.V injection of either tramadol or fentanyl produced significant increase in pain tolerance. I.V naloxone 30 min. before adminstration of either tramadol or fentanyl partially blocked the analgesic effect of tramadol, while the analgesic effect of fentanyl was completely blocked. These results suggested that both tramadol and fentanyl have a significant anti-hyperglycemic effect. This effect could be through activation of MOP receptors which may be mediated through increased glycogen deposition in the liver