title: 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 Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Rats were randomly divided into four groups: control, Δ(9)-THC, diabetes and diabetes + Δ(9)-THC groups. Diabetic rats were treated with a single dose of nicotinamide (85 mg/kg) 15 min before injection of streptozotocin (65 mg/kg). Δ(9)-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 Δ(9)-THC injections, pancreatic tissues were removed. Blood glucose levels and body weights of diabetic rats treated with Δ(9)-THC did not show statistically significant changes when compared with the diabetic animals on days 7, 14 and 21. Treatment with Δ(9)-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 Δ(9) -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 Δ(9)-THC may improve pancreatic cells via cannabinoid receptors in diabetes. The aim of present study was to elucidate the effects of Δ(9)-THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas. Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions. The curative effects of Δ(9)-THC can be occurred via activation of cannabinoid receptors in diabetic rat pancreas. Moreover, it may provide a protective effect against oxidative damage induced by diabetes. Thus, it is suggested that Δ(9)-THC can be a candidate for therapeutic alternatives of diabetes symptoms.
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Bilim University, Istanbul, Turkey; Department of Medical Biology, Faculty of Cerrahpasa Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Zeynep Mine
authors.initials: ZM
authors.lastname: Coskun
authors.forename: Sema
authors.initials: S
authors.lastname: Bolkent
mesh_terms: D000818:Animals; D001835:Body Weight; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009536:Niacinamide; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D009536:Niacinamide; D013311:Streptozocin; D013759:Dronabinol; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: cannabinoid receptors; gene expression; oxidative stress; type-2 diabetes; Δ9-THC