摘要
目的观察那格列酮对不同2型糖尿病模型动物的治疗及胰岛素增敏作用。方法那格列酮联合应用小剂量长效胰岛素(每只每日0.2 U,sc)治疗链佐菌素(150 mg·kg^(-1),ip)诱导的化学性糖尿病小鼠,观察那格列酮的胰岛素直接增敏作用;那格列酮ig,8 wk,分别采用ONE TOUCH稳豪型血糖测定仪及病理组织学检查,观察受试药物对自发性糖尿病小鼠(DB/DB小鼠)血糖及相关脏器(心脏、肾脏、胰腺)的影响;应用卡一介苗(BCG)每只10 mg静脉注射造成大鼠免疫性胰岛素抵抗模型,采用正糖钳技术观察那格列酮对该模型动物的葡萄糖输注速率(GIR)的回升作用。结果那格列酮(15,45,150 mg·kg^(-1)·d^(-1))合并应用胰岛素后,各剂量组动物的空腹血糖较CMC联合胰岛素对照组分别降低(14±s 4)%,(55±24)%,and(28±7)%。通过8 wk的治疗,那格列酮(15,45,150 mg·kg^(-1)·d^(-1))治疗组DB/DB小鼠的空腹血糖值与模型组相比有明显下降(P<0.01);病理组织学检查结果表明那格列酮明显改善糖尿病DB/DB小鼠肾脏和胰腺组织的损害。那格列酮(10,30,100 mg·kg^(-1)·d^(-1))连续给药2 wk,能明显升高免疫胰岛素抵抗模型大鼠高胰岛素状态下GIR(P<0.01)。结论那格列酮具有胰岛素直接增敏作用,对多种胰岛素抵抗动物模型均有治疗作用。
AIM To assess antidiabetic and insulin sensitizing effect of a novel thiazolidinedione, neoglitazone, in different animal models of type 2 diabetes. METHODS Neoglitazone combined with low-dose insulin （0.2 U.d-1 per mouse, sc） were given in streptozotocin （STZ） -induced diabetic mice for 7 d to inspect its insulin-sensitive improvement. The antidiabetic effect of chronic oral treatment （8 wk） with neoglitazone on spontaneous diabetes mice （DB/DB mice） was examined. The levels of blood glucose were measured by a One- Touch blood glucose meter and pathology of heart, kidney, and pancreas tissues were observed under a light microscope. The hyperinsulinaemic-euglycaemic clamp technique was applied to measure the increase of glucose infusion rate （GIR） of neoglitazone on the immune insulin-resistant rats induced by Bacillus Calmette-Guerin vaccine （10 mg per rat） . RESULTS Neoglitazone （15, 45, and 150 mg·kg^-1 ·d^-1） -insulin combination therapy decreased （14 ± s 4） %, （55 ± 24） %, and （28 ± 7） % of blood glucose levels compared with CMC-Na＋insulin group, respectively （P 〈 0.01） . In DB/DB mice, neoglitazone showed better reduction in blood glucose levels than those of model animals （P 〈 0.01） , and pathological studies indicated that neoglitazone attenuated the diabetic kidney and pancreas lesions. During a hyperinsulinaemic-euglycaemic clamp, neoglitazone （10, 30, and 100 mg· kg^-1·d^-1, ig for 2 wk） -treated groups required significantly higher GIR to maintain basal glucose concentrations than model group （P 〈 0.01） . CONCLUSION Neoglitazone could directly enhance insulin sensitivity and ameliorate insulin resistance in different diabetic animal models.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2008年第9期652-659,共8页
Chinese Journal of New Drugs and Clinical Remedies
关键词
那格列酮
糖尿病
2型
模型
动物
胰岛素敏感性
正楷钳
neoglitazone
diabetes mellitus, type 2
models, animal
insulin sensitivity
a hyperinsulinaemic-euglycaemic clamp
