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(英文)

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。

Antidiabetic and insulin-sensitizing effects of neoglitazone in different animal models of type 2 diabetes

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(0.2U·d-1 per mouse,sc)were given in streptozotiocin (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 therapy decreased ( 14±s4)%, (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,neoglitaxone(10,30,and 100mg·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.