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

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

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。

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·kg -1 ·d -1 and metformin 300 mg·kg -1 ·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.