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罗格列酮和二甲双胍对高脂饮食大鼠胰岛素抵抗的影响

[Effects of rosiglitazone and metformin on insulin resistance in high-fat diet rats].

作者信息

Chen Xiao-ping, Yang Wen-ying, Bu Shi, Xiao Jian-zhong, Liu Xue-li, Wang Na, Zhao Wen-hui

机构信息

Department of Endocrinology, Beijing China-Japan Friendship Hospital, Beijing 100029, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2004 Apr;43(4):280-3.

Abstract

OBJECTIVE

To observe the effects of rosiglitazone and metformin in rats on insulin resistance induced by high-fat diet.

METHODS

Normal 8-week old male SD rats were divided into four groups. They were normal chow group (NC, n = 11), high-fat diet (HF, n = 11), metformin-treated (HF + Met, n = 11) and rosiglitazone-treated group (HF + Ros, n = 11). Rosiglitazone 3 mg x kg(-1) x d(-1) and metformin 300 mg x kg(-1) x d(-1) were given orally to HF + Ros and HF + Met group, respectively. After feeding for 8 weeks, serum insulin, adiponectin, glucose (BG), triglyceride (TG) and free fatty acid (FFA) were measured in all the rats. Insulin sensitivity was measured with glucose infusion rate (GIR) and determined by using euglycemic-hyperinsulinemic clamp method.

RESULTS

High-fat diet induced obesity in SD rats after feeding for 8 weeks. High-fat diet decreased adiponectin level by 43.7% (P < 0.01) and GIR by 51.3% (P < 0.01) as compared with the NC group. Metformin decreased body weight by 8.4% (P < 0.01) and TG level by 40.5% (P < 0.01). Metformin significantly increased GIR by 58.9% (P < 0.01) when compared with the HF group. Rosiglitazone caused an apparent reduction of FFA (-25.3%, P < 0.05) and TG level (-54.0%, P < 0.01). At the same time, rosiglitazone increased adiponectin by 60% (P < 0.01), and improved insulin sensitivity by 149.6% (P < 0.01) as compared with the HF group.

CONCLUSIONS

(1) High-fat diet induces insulin resistance in SD rats; this was associated with an increase in visceral fat and a decrease in the level of adiponectin; (2) Metformin treatment improved insulin sensitivity accompanied by a decrease in body weight and TG level; (3) Rosiglitazone treatment ameliorates IR in a greater extent and is accompanied by a reduction of FFA, TG and an increase of adiponectin levels.

摘要

目的

观察罗格列酮和二甲双胍对高脂饮食诱导的大鼠胰岛素抵抗的影响。

方法

将8周龄正常雄性SD大鼠分为四组。分别为正常饮食组(NC,n = 11)、高脂饮食组(HF,n = 11)、二甲双胍治疗组(HF + Met,n = 11)和罗格列酮治疗组(HF + Ros,n = 11)。分别给予HF + Ros组和HF + Met组口服罗格列酮3 mg·kg⁻¹·d⁻¹和二甲双胍300 mg·kg⁻¹·d⁻¹。喂养8周后,测定所有大鼠的血清胰岛素、脂联素、血糖(BG)、甘油三酯(TG)和游离脂肪酸(FFA)。用葡萄糖输注速率(GIR)测定胰岛素敏感性,并采用正常血糖高胰岛素钳夹法进行测定。

结果

高脂饮食喂养8周后可诱导SD大鼠肥胖。与NC组相比,高脂饮食使脂联素水平降低43.7%(P < 0.01),GIR降低51.3%(P < 0.01)。二甲双胍使体重降低8.4%(P < 0.01),TG水平降低40.5%(P < 0.01)。与HF组相比,二甲双胍使GIR显著升高58.9%(P < 0.01)。罗格列酮使FFA明显降低(-25.3%,P < 0.05),TG水平降低(-54.0%,P < 0.01)。同时,与HF组相比,罗格列酮使脂联素升高60%(P < 0.01),胰岛素敏感性提高149.6%(P < 0.01)。

结论

(1)高脂饮食可诱导SD大鼠胰岛素抵抗;这与内脏脂肪增加和脂联素水平降低有关;(2)二甲双胍治疗可改善胰岛素敏感性,同时体重和TG水平降低;(3)罗格列酮治疗在更大程度上改善胰岛素抵抗,同时FFA、TG降低,脂联素水平升高。

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