You Mi-Kyoung, Kim Hwa-Jin, Rhyu Jin, Kim Hyeon-A
Department of Food and Nutrition / Research Institute of Human Ecology, Mokpo National University, 1666, Yeongsan-ro, Cheonggye-myeon, Muan-gun, Jeonam 58554, Korea.
Nutr Res Pract. 2017 Jun;11(3):198-205. doi: 10.4162/nrp.2017.11.3.198. Epub 2017 Apr 9.
BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of α-glucosidase has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice.
MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice.
In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, (Tyr)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 (Tyr)/IRS, whereas, down-regulated p-IRS-1 (Ser)/IRS.
Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.
背景/目的：梨通过抑制α-葡萄糖苷酶展现出抗糖尿病活性。然而，关于梨对肥胖状态下胰岛素信号通路的影响鲜有报道。本研究旨在探究梨渣50%乙醇提取物（PPE）能否改善胰岛素敏感性，并阐明其在3T3-L1细胞和高脂饮食（HFD）喂养的C57BL/6小鼠中的作用机制。
材料/方法：检测3T3-L1细胞中的脂质积累、单核细胞趋化蛋白-1（MCP-1）分泌和葡萄糖摄取。小鼠喂食高脂饮食（脂肪提供60%的热量），并每天口服一次PPE，持续8周，然后测量体重、胰岛素抵抗稳态模型评估（HOMA-IR）和血脂。通过蛋白质免疫印迹法评估3T3-L1细胞和小鼠脂肪组织中胰岛素信号通路相关蛋白的表达。
在3T3-L1细胞中，PPE在不影响细胞活力和脂质积累的情况下，抑制了MCP-1分泌，改善了葡萄糖摄取，并增加了磷酸化胰岛素受体底物1 [p-IRS-1, (Tyr)]、p-Akt和葡萄糖转运蛋白4（GLUT4）的蛋白表达。此外，在高脂饮食喂养的小鼠中，PPE降低了体重、HOMA-IR以及包括甘油三酯和低密度脂蛋白胆固醇在内的血脂。此外，在脂肪组织中，PPE上调了GLUT4的表达以及p-IRS-1 (Tyr)/IRS的表达比例，而下调了p-IRS-1 (Ser)/IRS。
我们的结果共同表明，PPE通过刺激胰岛素信号通路改善了3T3-L1细胞中的葡萄糖摄取以及高脂饮食喂养小鼠的胰岛素敏感性。此外，PPE诱导的胰岛素敏感性改善并未伴随着脂质积累。
