Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ9-THC

Abstract

The objectives of study were (a) to determine alteration of feeding, glucose level and oxidative stress and (b) to investigate expression and localization of cannabinoid receptors in type-2 diabetic rat pancreas treated with Δ9-tetrahydrocannabinol (Δ9-THC). Rats were randomly divided into four groups: control, Δ9-THC, diabetes and diabetes + Δ9-THC groups. Diabetic rats were treated with a single dose of nicotinamide (85 mg/kg) 15 min before injection of streptozotocin (65 mg/kg). Δ9-THC was administered intraperitoneally at 3 mg/kg/day for 7 days. Body weights and blood glucose level of rats in all groups were measured on days 0, 7, 14 and 21. On day 15 after the Δ9-THC injections, pancreatic tissues were removed. Blood glucose levels and body weights of diabetic rats treated with Δ9-THC did not show statistically significant changes when compared with the diabetic animals on days 7, 14 and 21. Treatment with Δ9-THC significantly increased pancreas glutathione levels, enzyme activities of superoxide dismutase and catalase in diabetes compared with non-treatment diabetes group. The cannabinoid 1 receptor was found in islets, whereas the cannabinoid 2 receptor was found in pancreatic ducts. Their localization in cells was both nuclear and cytoplasmic. We can suggest that Δ9-THC may be an important agent for the treatment of oxidative damages induced by diabetes. However, it must be supported with anti-hyperglycaemic agents. Furthermore, the present study for the first time emphasizes that Δ9-THC may improve pancreatic cells via cannabinoid receptors in diabetes.