再者，由于在β细胞中没有GLT5的表达，果糖不像葡萄糖一样可以刺激胰岛素的释放（16）。大量果糖在肝脏的堆积导致快速的脂肪生成和甘油三酯的积累，从而反过来又降低了胰岛素的敏感度并促进了肝脏胰岛素拮抗和糖耐量（3）。最近的一项研究成果表明果糖不能刺激胰岛素和瘦素的分泌且会减轻餐后ghrelin的抑制作用，据此人们怀疑长期摄入大量的果糖会导致热量摄入量的增加和促进体重增加和肥胖（17）。

大鼠模型
对啮齿动物来说， 高果糖膳食可在Sprague-Dawley (SD)大鼠 (8-10), Wistar 大鼠 (11, 12)和仓鼠(13, 14)中引起高甘油三酯血症，胰岛素拮抗和高血压。SD (18) 和Wistar大鼠 (19)都是已设立的蔗糖诱导胰岛素拮抗和高甘油三酯血症模型。当这些动物饲喂高达65%（重量比）蔗糖（相对于65%玉米淀粉）的饲料时，症状可以在短短2周内显现。研究已证明，导致代谢综合征的高蔗糖膳食中的活跃成分是果糖而非葡萄糖；同等数量的葡萄糖或淀粉并不会诱导这些症状（20-22）。除非长时间使用，这些高糖饲料并不会引起过多的体重増加（11）。

除了诱导代谢综合征之外，高果糖膳食还会在SD大鼠中引起肾脏肥大、传入小动脉增厚、肾小球高血压、皮质血管收缩等症状（23）。SD大鼠食用60%果糖饲料10周后便呈现出高甘油三酯血症、高胰岛素血症和更有甚者，高尿酸血症（20）。尿酸一直被人们认为在代谢综合征的发生中有一席之地，它可以抑制一氧化氮生物利用度，而一氧化氮在胰岛素刺激葡萄糖摄取的过程中是必须的。在摄取高果糖的动物中降低尿酸可以防止或逆转代谢综合征的某些症状如高胰岛素血症、收缩期高血压、高甘油三酯血症和体重增加（20）。此外，Shapiro等人最近证明，长期喂食果糖可在SD大鼠中诱导瘦素拮抗和加速高脂诱导肥胖症的发生（24）。与SD大鼠相近，以66％果糖饲料喂养超过10个星期的Wistar大鼠显示了上升收缩压和舒张压、脉压（血管硬度指数之一）增大等症状（12）。在高果糖饲料中加入长链（n - 3）多不饱和脂肪酸后，代谢和血管障碍消失（12）。

仓鼠模型
叙利亚金黄仓鼠（Mesocricetus auratus）是一种广泛使用脂蛋白研究模型，由于仓鼠血浆中胆固醇的主要载体是LDL（不同于大鼠），其脂蛋白代谢似乎与人类的最为相近（25）。仓鼠在食用高果糖饲料的情况下可发展高胰岛素血症、高甘油三酯血症和胰岛素拮抗等症状（13）。与大鼠相似，食用高果糖私饲料（60%能量）的仓鼠可以在2周内就表现出这些症状（13，14）。由于其肝脏高血浆脂蛋白生产过剩，以果糖喂养的仓鼠模型具有高水平的极低密度脂蛋白和载脂蛋白B的特征（14）。有趣的是，与那些食用高果糖饲料的仓鼠比较，食用高蔗糖饲料的仓鼠并无高水平的甘油三酯，且只表现出轻微胰岛素拮抗（13）。蔗糖只有一半是果糖，由此看来，仓鼠膳食中的果糖水平对胰岛素拮抗和高甘油三酯的快速发生是非常重要的。

小鼠模型
与大鼠和仓鼠相反，小鼠模型在蔗糖/果糖诱导胰岛素拮抗和高甘油三酯的研究中并不常用。小鼠对高蔗糖/果糖的反应各品系不一（26）。那些常用的品系如C57B1/6 小鼠要么不发展胰岛素拮抗，要么发展得很慢（27）。当C57Bl/6 小鼠和 Wistar 大鼠同样被高果糖灌胃3周后，C57Bl/6 小鼠与Wistar大鼠相比有更低水平的血浆甘油三酯和胆固醇，呈现出一个被认为对心血管系统更健康的生化轮廓（28）。另一方面，当 C57/BL6小鼠喂饲高果糖膳食8周后，他们呈现出平均动脉压上升、葡萄糖耐受性降低和血浆胆固醇增加等症状，这些症状的发生归因于是由于交感系统和血管紧张素系统的激活（29）。此外，Cunha等人发现，C57/BL6小鼠高果糖喂养12周后会产生肾功能损害，具体症状为尿蛋白和尿排泄量的增加（30）。然而，小鼠基因组比起大鼠的更容易操作，几个基因敲除模型（容易产生动脉粥样硬化）也对高果糖膳食产生甘油三酯升高的反应（31）。

因此，具体根据所选择的啮齿目动物模型而定，高果糖/糖膳食可复制人类代谢综合征的某几个方面，如高甘油三酯血症、高血压和高胰岛素血症。

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