Rafailovska Elena, Xhemaili Elona, Naumovska Zorica, Gigopulu Olga, Miova Biljana, Suturkova Ljubica, Stefkov Gjoshe
Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 3, 1000 Skopje, North Macedonia.
Department of Pharmacy, Faculty of Medical Sciences, University of Tetovo, Ilinden bb, 1200 Tetovo, North Macedonia.
Pharmaceuticals (Basel). 2025 Mar 21;18(4):446. doi: 10.3390/ph18040446.
: Diabetes mellitus is a growing global health concern, driving the exploration of new therapies like cannabidiol (CBD), which shows potential in improving insulin sensitivity and glycemic control, though its effects on glucose metabolism remain unclear. This study evaluates CBD's dose-dependent effects on glycemia, insulin, and hepatic carbohydrate metabolism in diabetic rats. : The Oral Glucose Tolerance Test (OGTT) was performed in healthy rats to compare intragastric vs. intraperitoneal CBD (0.5, 5, 50 mg/kg). Diabetic rats were treated with intragastric CBD (25, 50, 100 mg/kg) or metformin (70 mg/kg) for 8 days. Blood glucose, insulin, lipid profiles, and key carbohydrate-metabolizing enzymes were analyzed. : In the OGTT, intragastric CBD reduced glycemic AUC, with 50 mg/kg showing the strongest effect, while intraperitoneal CBD had no impact. In diabetic rats, metformin and 25 mg/kg CBD lowered blood glucose, but only CBD increased insulin. The 50 mg/kg dose caused the greatest glucose reduction and moderate insulin rise, while 100 mg/kg had no effect. At 25 mg/kg, CBD inhibited glucose-6-phosphatase and increased glucose-6-phosphate. The 50 mg/kg dose further suppressed gluconeogenic enzymes, reduced glycogen phosphorylase and liver glucose, and enhanced glucose-6-phosphate, showing the strongest metabolic effects. The 100 mg/kg dose increased hexokinase but had weaker metabolic effects. Metformin improved glucose utilization and glycogen storage. CBD at 25 and 50 mg/kg reduced triacylglycerols and increased HDL, while 100 mg/kg had no effect. This study provides strong evidence of CBD's antidiabetic potential, especially at 50 mg/kg, particularly through its modulation of glucose metabolism and tendency to regulate insulin levels.
糖尿病是一个日益引起全球健康关注的问题，促使人们探索像大麻二酚（CBD）这样的新疗法，尽管其对葡萄糖代谢的影响尚不清楚，但它在改善胰岛素敏感性和血糖控制方面显示出潜力。本研究评估了CBD对糖尿病大鼠血糖、胰岛素和肝脏碳水化合物代谢的剂量依赖性影响。：对健康大鼠进行口服葡萄糖耐量试验（OGTT），以比较胃内给药与腹腔注射CBD（0.5、5、50mg/kg）的效果。糖尿病大鼠接受胃内注射CBD（25、50、100mg/kg）或二甲双胍（70mg/kg）治疗8天。分析血糖、胰岛素、血脂谱和关键碳水化合物代谢酶。：在OGTT中，胃内注射CBD降低了血糖曲线下面积（AUC），50mg/kg的效果最强，而腹腔注射CBD则没有影响。在糖尿病大鼠中，二甲双胍和25mg/kg的CBD降低了血糖，但只有CBD增加了胰岛素。50mg/kg的剂量导致最大程度的血糖降低和适度的胰岛素升高，而100mg/kg则没有效果。在25mg/kg时，CBD抑制葡萄糖-6-磷酸酶并增加葡萄糖-6-磷酸。50mg/kg的剂量进一步抑制糖异生酶，降低糖原磷酸化酶和肝脏葡萄糖，并增强葡萄糖-6-磷酸，显示出最强的代谢作用。100mg/kg的剂量增加了己糖激酶，但代谢作用较弱。二甲双胍改善了葡萄糖利用和糖原储存。25mg/kg和50mg/kg的CBD降低了三酰甘油并增加了高密度脂蛋白（HDL），而100mg/kg则没有效果。 本研究提供了强有力的证据证明CBD的抗糖尿病潜力，特别是在50mg/kg时，尤其是通过其对葡萄糖代谢的调节和调节胰岛素水平的趋势。
