Exenatide improves insulin sensitivity of insulin resistant rats by decreasing plasma adiponectin and increasing leptin levels

谭兴容; 杨刚毅; 李伶; 王毅; 方超; 李生兵; 李钶

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Exenatide improves insulin sensitivity of insulin resistant rats by decreasing plasma adiponectin and increasing leptin levels

更新时间：2026-01-09

- Exenatide improves insulin sensitivity of insulin resistant rats by decreasing plasma adiponectin and increasing leptin levels
- Journal of Army Medical University Vol. 32, Issue 20, Pages: 2201-2204(2010)
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  CLC： R589;R363.27;R977.6
- Published：2010
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谭兴容,杨刚毅,李伶,王毅,方超,李生兵,李钶.Exenatide对胰岛素抵抗大鼠胰岛素敏感性及脂联素、瘦素水平的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(20):2201-2204.

　Tan Xingrong,Yang Gangyi,Li Ling,Wang Yi,Fang Chao,Li Shengbing,Li Ke.Exenatide improves insulin sensitivity of insulin resistant rats by decreasing plasma adiponectin and increasing leptin levels[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(20):2201-2204.
谭兴容,杨刚毅,李伶,王毅,方超,李生兵,李钶.Exenatide对胰岛素抵抗大鼠胰岛素敏感性及脂联素、瘦素水平的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(20):2201-2204. DOI：

　Tan Xingrong,Yang Gangyi,Li Ling,Wang Yi,Fang Chao,Li Shengbing,Li Ke.Exenatide improves insulin sensitivity of insulin resistant rats by decreasing plasma adiponectin and increasing leptin levels[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(20):2201-2204. DOI：

摘要

目的探讨Exenatide对高脂诱导胰岛素抵抗（insulin resistance，IR）大鼠胰岛素敏感性及血浆脂联素、瘦素水平的影响。方法将69只清洁级健康雄性（SD）大鼠分为对照组（NC组

n=22）

高脂组（HF组

n=23）

Exenatide治疗组（HE组，n=24）。高脂诱导胰岛素抵抗大鼠给予Exenatide 10周后，采用扩展胰岛素钳夹技术测定机体胰岛素敏感性和糖脂代谢，并观察血浆脂联素、瘦素水平的变化。结果高脂诱导IR大鼠经Exenatide处理（HE组）后， Lee’s指数、空腹血浆游离脂肪酸（FFA）、甘油三酯（TG）、总胆固醇酯（TC）、低密度脂蛋白（LDL）明显降低（P0.01），高密度脂蛋白（HDL）明显升高（P0.01）。同时，HE组血浆脂联素水平明显升高（P0.01），瘦素水平明显降低（P0.01）。在钳夹稳态时，高脂组（HF）与对照组（NC）相比，血浆FFA、胰岛素（INS）水平均明显升高（P0.01），葡萄糖输注率（GIR）、葡萄糖清除率（G

）明显降低（P0.01），且胰岛素对肝糖输出（HGP）的抑制作用明显障碍（仅抑制16%）。经Exenatide处理后，血浆FFA、INS水平则明显降低（P0.01），G

、GIR明显升高（P0.01），胰岛素对HGP的抑制作用明显增强（抑制67%）。结论 Exenatide处理可能通过下调血浆瘦素水平和上调血浆脂联素水平，改善糖脂代谢而使机体胰岛素敏感性增加。

Abstract

Objective To investigate the effects of exenatide on the plasma levels of adiponectin (ADI) and leptin (LEP) and on insulin sensitivity in insulin resistant rats induced by high fat diet. Methods A total of 69 health male rats were divided into control group (n=22

normal chow)

and high fat group (n=23

high fat diet) and exenatide treatment group (n=24

igh fat diet with exenatide treatment). All rats were fed with corresponding diet for 20 weeks. Insulin resistance was found in 2 later groups after 10 weeks’ high fat diet

and then exenatide (2 μg/kg

twice a day) or normal saline (at same volume and time) were injected for 10 weeks. The insulin sensitivity and glucose lipid metabolism in awaken rats were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3-[

]

glucose as a tracer. In addition

plasma ADI and leptin levels were measured by ELISA. Results Plasma free fatty acids (FFA)

triglyceride (TG)

total cholesterol (TC)

and low density lipoprotein (LDL) levels were significantly reduced in high fat rats after exenatide treatment (P0.01)

however plasma high density lipoprotein (HDL) level were significantly increased in exenatide treatment group (P0.01). In addition

plasma leptin levels was also significantly reduced

and plasma ADI levels was significantly increased in exenatide treatment group (P0.01). During the clamp steady-state

there was a significant increase in plasma FFA and insulin and a significant decrease in glucose infusion rate (GIR)

glucose disposal rate (G

) in high fat group compared to control group (P0.01). The suppressive effect of insulin on hepatic glucose production (HGP) was significantly blunted (only 16%) in high fat group. In exenatide treatment group

plasma insulin and FFA levels were significantly decreased (P0.01)

GIR and G

were significantly increased (P0.01)

and HGP was suppressed by 67%. Conclusion Exenatide treatment may ameliorate high fat diet-induced insulin resistance by reducing leptin level

elevating adiponectin level and thus improving glucose-lipid metabolism.

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