23-乙酰泽泻醇B对2型糖尿病小鼠血糖的影响

Influence of alisol B 23-acetate on blood glucose in type 2 diabetic mice

目的探讨23-乙酰泽泻醇B是否有治疗2型糖尿病的潜能。方法通过腹腔注射链脲佐菌素和烟酰胺建立2型糖尿病小鼠模型。灌胃罗格列酮或23-乙酰泽泻醇B 3周后,测定2型糖尿病小鼠血糖值,次日进行口服葡萄糖耐受试验(OGTT)。采用葡萄糖荧光示踪剂,测定23-乙酰泽泻醇B对葡萄糖吸收的影响。采用3T3-L1前脂肪细胞分化模型,测定其对分化的影响。结果分别每天灌胃阳性药罗格列酮10 mg·kg^(-1)、23-乙酰泽泻醇B(5、10、20 mg·kg^(-1)),连续灌胃给药3周后,降低了2型糖尿病小鼠血糖值,一定程度改善OGTT过程中胰岛素抵抗。在30 mmol·L^(-1)高糖条件下,23-乙酰泽泻醇B促进了脂肪细胞对胰岛素刺激的葡萄糖吸收;23-乙酰泽泻醇B(1、10μmol·L^(-1))促进3T3-L1前脂肪细胞的分化过程。结论 23-乙酰泽泻醇B降低2型糖尿病小鼠血糖,促进前脂肪细胞分化,促进脂肪细胞吸收葡萄糖,但作用机制仍需进一步探索。

Aim To explore whether alisol B 23-acetate possesses the therapeutic potential for treatment of type 2 diabetes mellitus(T2DM). Methods T2DM mouse model was established by combined administration of streptozotocin and nicotinamide.After three weeks of oral administration of rosiglitazone or alisol B 23-acetate,the blood glucose of type 2 diabetic mice was measured.Oral glucose tolerance test(OGTT) was carried out the next day.Rosiglitazone was chosen as positive drug.2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose(2-NBDG) uptake assay in adipocytes was adopted to test whether alisol B 23-acetate had effect on glucose uptake in cells.3T3-L1 pre-adipocytes differentiation model was performed to evaluate whether alisol B 23-acetate promoted adipogenesis. Results Mice exhibited significantly higher blood glucose concentration after intraperitoneal injection of streptozotocin and nicotinamide for three weeks,as examined by blood glucose concentration on day 21 and OGTT on day 22,compared with normal mice in blank control group.After orally administrating alisol B 23-acetate at dose of 5 mg·kg-1 ,10 mg·kg-1 ,20 mg·kg-1 daily for three weeks,respectively,or orally administered rosiglitazone at dose of 10 mg·kg-1 daily for three weeks,blood glucose greatly decreased in type 2 diabetic mice.Moreover,insulin resistance was also improved to a certain degree during OGTT.Furthermore,alisol B 23-acetate not only increased insulin-induced glucose uptake in adipocytes at the concentration of 30 mmol·L-1 glucose,but also accelerated 3T3-L1 pre-adipocytes differentiation process at concentration of 1 μmol·L-1 and 10 μmol·L-1 . Conclusions Alisol B 23-acetate reduces blood glucose of type 2 diabetic mice,promotes pre-adipocyte differentiation and increases glucose uptake in adipocytes;however,the mechanism of action needs further exploration.