Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, One Shields Ave., Davis, CA 95616, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1343-50. doi: 10.1152/ajpregu.00468.2009. Epub 2010 Feb 10.
Sustained fructose consumption has been shown to induce insulin resistance and glucose intolerance, in part, by promoting oxidative stress. Alpha-lipoic acid (LA) is an antioxidant with insulin-sensitizing activity. The effect of sustained fructose consumption (20% of energy) on the development of T2DM and the effects of daily LA supplementation in fructose-fed University of California, Davis-Type 2 diabetes mellitus (UCD-T2DM) rats, a model of polygenic obese T2DM, was investigated. At 2 mo of age, animals were divided into three groups: control, fructose, and fructose + LA (80 mg LA.kg body wt(-1).day(-1)). One subset was followed until diabetes onset, while another subset was euthanized at 4 mo of age for tissue collection. Monthly fasted blood samples were collected, and an intravenous glucose tolerance test (IVGTT) was performed. Fructose feeding accelerated diabetes onset by 2.6 +/- 0.5 mo compared with control (P < 0.01), without affecting body weight. LA supplementation delayed diabetes onset in fructose-fed animals by 1.0 +/- 0.7 mo (P < 0.05). Fructose consumption lowered the GSH/GSSG ratio, while LA attenuated the fructose-induced decrease of oxidative capacity. Insulin sensitivity, as assessed by IVGTT, decreased in both fructose-fed and fructose + LA-supplemented rats. However, glucose excursions in fructose-fed LA-supplemented animals were normalized to those of control via increased glucose-stimulated insulin secretion. Fasting plasma triglycerides were twofold higher in fructose-fed compared with control animals at 4 mo, and triglyceride exposure during IVGTT was increased in both the fructose and fructose + LA groups compared with control. In conclusion, dietary fructose accelerates the onset of T2DM in UCD-T2DM rats, and LA ameliorates the effects of fructose by improving glucose homeostasis, possibly by preserving beta-cell function.
持续摄入果糖已被证明会导致胰岛素抵抗和葡萄糖耐量降低，部分原因是促进氧化应激。α-硫辛酸（LA）是一种具有胰岛素增敏作用的抗氧化剂。本研究旨在探讨持续摄入果糖（占能量的 20%）对 2 型糖尿病（T2DM）发展的影响，以及 LA 每日补充对果糖喂养的加利福尼亚大学 2 型糖尿病（UCD-T2DM）大鼠的影响，该模型是多基因肥胖 2 型糖尿病的模型。动物在 2 月龄时分为 3 组：对照组、果糖组和果糖+LA 组（80mg LA.kg 体重-1.d-1）。一部分动物一直随访至糖尿病发病，另一部分动物在 4 月龄时安乐死用于组织采集。每月采集禁食血样，进行静脉葡萄糖耐量试验（IVGTT）。与对照组相比，果糖喂养使糖尿病发病提前 2.6+/-0.5 个月（P<0.01），而不影响体重。LA 补充使果糖喂养动物的糖尿病发病时间延迟 1.0+/-0.7 个月（P<0.05）。果糖摄入降低了 GSH/GSSG 比值，而 LA 减弱了果糖引起的氧化能力下降。IVGTT 评估的胰岛素敏感性在果糖喂养和果糖+LA 补充的大鼠中均降低。然而，通过增加葡萄糖刺激的胰岛素分泌，果糖喂养 LA 补充的动物的血糖波动得到了正常化。4 月龄时，果糖喂养组的空腹血浆甘油三酯是对照组的两倍，并且在 IVGTT 期间，果糖组和果糖+LA 组的甘油三酯暴露均高于对照组。综上所述，饮食果糖加速了 UCD-T2DM 大鼠 T2DM 的发病，而 LA 通过改善葡萄糖稳态，可能通过保护β细胞功能，改善果糖的作用。
