芒果苷对果糖诱导的代谢综合征大鼠模型胰岛素抵抗的缓解作用与骨骼肌中CD36重新分布的调节有关。
Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle.
作者信息
Zhou Liang, Pan Yongquan, Chonan Ritsu, Batey Robert, Rong Xianglu, Yamahara Johji, Wang Jianwei, Li Yuhao
机构信息
Faculty of Basic Medical Sciences (L.Z.), Laboratory Animal Center (Y.P.), and Laboratory of Traditional Chinese Medicine (J.W.), Chongqing Medical University, Chongqing, China; Koei Kogyo Co., Ltd., Tokyo, Japan (R.C.); Central Clinical School, Royal Prince Alfred Hospital, The University of Sydney, Sydney, Australia (R.B.); Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, and the Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China (X.R.); Pharmafood Institute, Kyoto, Japan (J.Y.); and Endocrinology and Metabolism Group, Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, Australia (Y.L.).
Faculty of Basic Medical Sciences (L.Z.), Laboratory Animal Center (Y.P.), and Laboratory of Traditional Chinese Medicine (J.W.), Chongqing Medical University, Chongqing, China; Koei Kogyo Co., Ltd., Tokyo, Japan (R.C.); Central Clinical School, Royal Prince Alfred Hospital, The University of Sydney, Sydney, Australia (R.B.); Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, and the Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China (X.R.); Pharmafood Institute, Kyoto, Japan (J.Y.); and Endocrinology and Metabolism Group, Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, Australia (Y.L.)
出版信息
J Pharmacol Exp Ther. 2016 Jan;356(1):74-84. doi: 10.1124/jpet.115.229005. Epub 2015 Oct 23.
Mangiferin is one of the prominent active components responsible for the antidiabetic property of many traditional herbs, but its underlying mechanisms of action remain unclear. CD36 in skeletal muscle is known to contribute to the etiology of insulin resistance by facilitating fatty acid uptake. This study investigated the effect of mangiferin on insulin resistance. The results showed that treatment of Wistar-Kyoto rats with mangiferin (15 mg/kg, once daily, by oral gavage) for 7 weeks inhibited chronic liquid fructose consumption-induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test (OGTT), and the homeostasis model assessment of insulin resistance index. It also suppressed the increases in fasted plasma nonesterified fatty acid (NEFA) concentration and the adipose tissue insulin resistance index. Mechanistically, mangiferin neither affected intakes of fructose and chow, and the increase in epididymal and perirenal fat, nor attenuated fructose-induced hypertension. In contrast, mangiferin attenuated fructose-induced acceleration of plasma NEFA clearance during OGTT, and tended to decrease excessive triglyceride accumulation in gastrocnemius. Immunofluorescence staining and subsequent rating of CD36-expressing fibers in gastrocnemius revealed that mangiferin restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution. In addition, the effects of mangiferin on the parameters associated with insulin resistance and abnormal fatty acid metabolism were absent in the spontaneously hypertensive rats carrying numerous nonfunctional mutations in the CD36 gene. Thus, these results suggest that mangiferin treatment mitigates insulin resistance in a rat model of fructose-induced metabolic syndrome by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle.
芒果苷是许多传统草药具有抗糖尿病特性的主要活性成分之一，但其潜在作用机制尚不清楚。已知骨骼肌中的CD36通过促进脂肪酸摄取而导致胰岛素抵抗的发生。本研究调查了芒果苷对胰岛素抵抗的影响。结果显示，用芒果苷（15毫克/千克，每日一次，经口灌胃）处理Wistar-Kyoto大鼠7周，可抑制慢性液体果糖摄入诱导的基线及口服葡萄糖耐量试验（OGTT）期间血浆胰岛素浓度升高，以及胰岛素抵抗指数的稳态模型评估。它还抑制了空腹血浆非酯化脂肪酸（NEFA）浓度和脂肪组织胰岛素抵抗指数的升高。从机制上讲，芒果苷既不影响果糖和食物的摄入量，也不影响附睾和肾周脂肪的增加，也不能减轻果糖诱导的高血压。相反，芒果苷减弱了OGTT期间果糖诱导的血浆NEFA清除加速，并倾向于减少腓肠肌中过多的甘油三酯积累。对腓肠肌中表达CD36的纤维进行免疫荧光染色及后续评分显示，芒果苷恢复了果糖刺激的肌膜CD36过表达，并减少了细胞内CD36的分布。此外，在CD36基因携带大量无功能突变的自发性高血压大鼠中，芒果苷对与胰岛素抵抗和异常脂肪酸代谢相关参数没有影响。因此，这些结果表明，芒果苷治疗通过调节骨骼肌中肌膜和细胞内CD36的重新分布，减轻了果糖诱导的代谢综合征大鼠模型中的胰岛素抵抗。
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