胰岛素敏化剂的组合,吡格列酮,长效GLP-1人类模拟liraglutide、施加强大的协同降糖疗效在严重糖尿病ZDF老鼠。

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拉森PJ,伍尔夫EM Gotfredsen CF、品牌CL, Sturis J, Vrang N,克努森磅,Lykkegaard K

胰岛素敏化剂的组合,吡格列酮,长效GLP-1人类模拟liraglutide、施加强大的协同降糖疗效在严重糖尿病ZDF老鼠。

糖尿病ob金属底座。2008年4月,10 (4):301 - 11。doi: 10.1111 / j.1463-1326.2008.00865.x。

PubMed ID

18333889 (在PubMed

]

文摘

摘要目的:严重的胰岛素抵抗和胰腺β细胞功能受损是2型糖尿病的病理生理因素,和理想情况下,应当同时解决antihyperglycaemic策略。研究设计和方法:疗效相结合的长效人类glucagon-like peptide-1 (GLP-1)模拟,liraglutide(0.4毫克/公斤/天),与胰岛素敏化剂,吡格列酮(10毫克/公斤/天),评估了在严重糖尿病Zucker糖尿病脂肪大鼠42天。对血糖控制的影响评估了糖化血红蛋白(HbA (1 c)) 28天,口服葡萄糖耐量试验在42天。结果:Liraglutide和吡格列酮协同改善血糖控制所反映的显著减少HbA (1 c) (Liraglutide +吡格列酮:4.8 + / - 0.3%;liraglutide: 8.8 + / - 0.6%;吡格列酮:7.9 + / - 0.4%;车辆:9.7 + / - 0.3%)和改进的口服葡萄糖耐量42天(曲线下的面积;liraglutide +吡格列酮:4244 + / - 445更易/ l x分钟;liraglutide: 7164 + / - 187更易与l x分钟;吡格列酮:7430 + / - 446更易与l x分钟; vehicle: 8093 +/- 139 mmol/l x min). A 24-h plasma glucose profile at day 38 was significantly decreased only in the liraglutide + pioglitazone group. In addition, 24-h insulin profile was significantly elevated only in the liraglutide + pioglitazone group. Liraglutide significantly decreased food intake alone and in combination with pioglitazone, while pioglitazone alone increased cumulated food intake. As a result, rats on liraglutide alone gained significantly less weight than vehicle-treated rats, whereas rats on pioglitazone alone gained significantly more body weight than vehicle-treated rats. However, combination therapy with liraglutide and pioglitazone caused the largest weight gain, probably reflecting marked improvement of energy balance because of reduction of glucosuria. CONCLUSIONS: Combination therapy with insulinotropic GLP-1 agonist liraglutide and insulin sensitizer, pioglitazone, improves glycaemic control above and beyond what would be expected from additive effects of the two antidiabetic agents.

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药物靶点

药物	目标	类	生物	药理作用	行动
Liraglutide	Glucagon-like肽受体1	蛋白质	人类	是的	受体激动剂	细节