Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice

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	Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice
	Choi, Woon-Seok ; Lee, Jung-Jin ; Kim, Yohan ; Kim, In-Su ; Zhang, Wei-Yun ; Myung, Chang-Seon ; Zhang WY(张伟云)
刊名	http://dx.doi.org/10.1007/s12272-011-0412-9
	2011-04
关键词	PROLIFERATOR-ACTIVATED RECEPTORS DIFFERENTIAL EXPRESSION CARDIOVASCULAR-DISEASE METABOLIC SYNDROME PANCREATIC-ISLETS GLYCEMIC CONTROL STREPTOZOTOCIN PPAR NICOTINAMIDE GLUCOSE
英文摘要	Ministry of Education, Science and Technology [2009-0093815]; NRF [2010-0014839]; Peroxisome proliferator-activated receptor (PPAR) a, which is abundant in the liver, increases lipoprotein lipase activity, resulting in a decrease of triglyceride (TG) levels. PPAR gamma, which is abundant in adipose tissue, stimulates adipocyte differentiation and adipogenesis, and results in an increase in insulin sensitivity. Fenofibrate, a PPAR alpha agonist, is commonly used to treat dyslipidemia, and rosiglitazone, a PPAR gamma agonist, is effective in improving glycemic control. To examine the synergistic effects of rosiglitazone in combination with fenofibrate, an obese type 2 diabetes mellitus (DM) mouse model was established by the combined administration of streptozotocin and nicotinamide and fed on a high-fat diet (35% of energy as fat) for 3 weeks. The mice had significantly higher plasma glucose concentrations and insulin resistance, as examined by an oral glucose tolerance test and insulin challenge test compared with normal mice. After establishing a dose-response curve for each drug, the drugs were orally administered for 3 weeks either alone or in combination. After individual administration of fenofibrate, HDL cholesterol levels significantly increased, and plasma glucose and TG levels decreased in obese type 2 DM mice. The individual administration of rosiglitazone showed increased insulin resistance (QUICKI). However, HDL cholesterol and TG levels were not significantly changed. In a combination of fenofibrate at 25 mg/kg and rosiglitazone at 1.25 mg/kg there was a decrease in plasma glucose and TG levels, and a combination of fenofibrate at 50 mg/kg and rosiglitazone at 2.5 mg/kg showed an increase in plasma HDL cholesterol levels. Moreover, parameters related to insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were improved significantly. Thus, our results show that combination therapy with lower doses of fenofibrate and rosiglitazone ameliorates the type 2 DM condition to a greater extent than high doses of either individual monotherapy.
语种	英语
出版者	ARCH PHARM RES
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/88454]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Choi, Woon-Seok,Lee, Jung-Jin,Kim, Yohan,et al. Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice[J]. http://dx.doi.org/10.1007/s12272-011-0412-9,2011.
APA	Choi, Woon-Seok.,Lee, Jung-Jin.,Kim, Yohan.,Kim, In-Su.,Zhang, Wei-Yun.,...&张伟云.(2011).Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice.http://dx.doi.org/10.1007/s12272-011-0412-9.
MLA	Choi, Woon-Seok,et al."Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice".http://dx.doi.org/10.1007/s12272-011-0412-9 (2011).