Rosiglitazone and fenofibrate improve insulin sensitivity of pre-diabetic OLETF rats by reducing malonyl-CoA levels in the liver and skeletal muscle.
Rosiglitazone and fenofibrate improve insulin sensitivity of pre-diabetic OLETF rats by reducing malonyl-CoA levels in the liver and skeletal muscle.
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DOI：
10.1016/j.lfs.2009.02.021
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发表时间：
2009-05-08
期刊：
影响因子：
6.1
通讯作者：
Ma ZA
中科院分区：
文献类型：
--
作者：
Zhao Z;Lee YJ;Kim SK;Kim HJ;Shim WS;Ahn CW;Lee HC;Cha BS;Ma ZA
罗格列酮和非诺贝特分别是过氧化物酶体增殖物激活受体-γ(PPARγ)和-α(PPARα)的特异性激动剂，可改善糖尿病动物和2型糖尿病患者的胰岛素敏感性。在这里，我们研究了喂食正常和高脂饮食的糖尿病前期大冢长埃文斯德岛脂肪(OLETF)大鼠对这些PPAR激动剂的反应。糖尿病前期OLETF大鼠接受高脂饲料或标准饲料加或不加罗格列酮或非诺贝特2周。测定大鼠的代谢及代谢组织中丙二酰辅酶A脱羧酶(MCD)、乙酰辅酶A羧基酶(ACC)和AMP活化蛋白激酶(AMPK)的活性。罗格列酮和非诺贝特显著改善了高脂饮食喂养的OLETF大鼠的胰岛素敏感性，降低了血浆甘油三酯和游离脂肪酸水平。非诺贝特特别降低高脂饮食OLETF大鼠的体重、脂肪和总胆固醇。罗格列酮或非诺贝特可显著降低OLETF大鼠骨骼肌和肝脏中升高的丙二酰辅酶A水平，部分原因是MCD活性和表达增加。另一方面，高脂饲料组大鼠骨骼肌ACC活性无明显变化，肝脏ACC活性降低。OLETF大鼠的AMPK活性显著降低，且不受这些激动剂的影响。这些结果表明，罗格列酮和非诺贝特治疗糖尿病前期OLETF大鼠，特别是那些喂食高脂饮食的大鼠，通过增加MCD的活性和降低肝脏和骨骼肌中的丙二酰辅酶A水平，显著改善了胰岛素敏感性和脂肪酸代谢。
Rosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα), respectively, improve insulin sensitivity in diabetic animals and in patients with type 2 diabetes. Here we investigated how pre-diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats fed with normal and high-fat diets respond to these PPAR agonists. Pre-diabetic OLETF rats were subjected to high-fat or standard diets with or without rosiglitazone or fenofibrate for 2 weeks. The metabolism of the rats and the levels of malonyl-CoA and activities of malonyl-CoA decarboxylase (MCD), acetyl-CoA carboxylase (ACC), and AMP-activated protein kinase (AMPK) in metabolic tissues were assessed. Rosiglitazone and fenofibrate significantly improved insulin sensitivity and reduced the levels of plasma triglycerides and free fatty acids in OLETF rats fed with a high-fat diet. Fenofibrate particularly reduced the body weight, fat, and total cholesterol in high fat diet OLETF rats. The highly elevated malonyl-CoA levels in the skeletal muscle and liver of OLETF rat were significantly reduced by rosiglitazone or fenofibrate due to, in part, the increased MCD activities and expression. On the other hand, ACC activities were unchanged in skeletal muscle and decreased in liver in high fat diet group. AMPK activities were dramatically decreased in OLETF rats and not affected by these agonists. These results demonstrate that treatment of pre-diabetic OLETF rats–particularly those fed a high-fat diet–with rosiglitazone and fenofibrate significantly improves insulin sensitivity and fatty acid metabolism by increasing the activity of MCD and reducing malonyl-CoA levels in the liver and skeletal muscle.
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影响因子：
4.1
作者：
Lee, GY;Kim, NH;Kim, YS
通讯作者：
Kim, YS
影响因子：
4.8
作者：
Guerre-Millo, M;Gervois, P;Staels, B
通讯作者：
Staels, B
影响因子：
5.1
作者：
KAWANO, K;HIRASHIMA, T;NATORI, T
通讯作者：
NATORI, T
影响因子：
3.9
作者：
Brownsey, RW;Boone, AN;Lee, WM
通讯作者：
Lee, WM
DOI：
10.1152/ajpregu.00002.2007
发表时间：
2007-07-01
影响因子：
2.8
作者：
Bi, Sheng;Chen, Jie;Moran, Timothy H.
通讯作者：
Moran, Timothy H.