罗格列酮和二甲双胍对高脂饲养造成的胰岛素抵抗的影响

目的　观察高脂饲养正常大鼠造成胰岛素抵抗 (IR)及不同药物干预的影响。方法将 8周龄雄性SD大鼠随机分为 4组 ,每组各 11只 :正常饲养组 (NC)、高脂饲养组 (HF)、高脂 二甲双胍组 (HF Met)、高脂 罗格列酮组 (HF Ros)。罗格列酮 3mg·kg-1·d-1或二甲双胍 30 0mg·kg-1·d-1剂量进行灌胃。饲养 8周时取空腹血测游离脂肪酸 (FFA)、甘油三酯 (TG)、脂联素等。胰岛素敏感性用正常血糖高胰岛素钳夹技术稳态时的葡萄糖输注率 (GIR)来评价。结果　高脂饲养 8周后 ,与NC组相比 ,HF组呈现肥胖 ,血浆脂联素水平低 4 3 7% (P <0 0 1) ,GIR低 5 1 3% (P <0 0 1)。HF Met组体重和TG均低于HF组 ,分别低 8 4 %和 4 0 5 % ,P值均 <0 0 1,GIR高5 8 9% (P <0 0 1)。HF Ros组FFA和TG均显著低于HF组 ,分别低 2 5 3% (P <0 0 5 )和 5 4 0 %(P <0 0 1) ,血浆脂联素水平高 6 0 % (P <0 0 1) ,GIR高 14 9 6 % (P <0 0 1)。结论　 (1)正常热量高脂饲养正常SD大鼠 8周可引起肥胖 ,血浆脂联素水平下降和胰岛素抵抗。 (2 )罗格列酮和二甲双胍均可显著改善高脂饲养引发的胰岛素抵抗。前者伴有显著血FFA、TG降低和脂联素升高 ,后者伴有体重及血TG降低。

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

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.