Milk-Derived Tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) Enhance Insulin Sensitivity and Prevent Insulin Resistance in 3T3-F442A Preadipocytes
Milk-Derived Tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) Enhance Insulin Sensitivity and Prevent Insulin Resistance in 3T3-F442A Preadipocytes
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DOI：
10.1021/acs.jafc.8b02051
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发表时间：
2018-10-03
影响因子：
6.1
通讯作者：
Wu, Jianping
中科院分区：
文献类型：
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作者：
Chakrabarti, Subhadeep;Jahandideh, Forough;Wu, Jianping
开发天然衍生化合物，特别是具有潜在的胰岛素增敏和/或预防胰岛素抵抗作用的生物活性多肽，引起了人们的极大兴趣。此前，我们展示了乳源三肽IPP(Ile-Pro-Pro)和VPP(Val-Pro-Pro)在培养的前脂肪细胞上的成脂和胰岛素模拟作用，以及它们先前已知的降压和抗炎功能。然而，这些多肽对胰岛素信号转导的影响尚不清楚。因此，我们研究了IPP和VPP对前脂肪细胞中胰岛素信号的影响，这是一个研究胰岛素信号的成熟模型。我们的结果表明，这两种多肽都增强了胰岛素信号转导，并有助于在肿瘤坏死因子(TNF)存在的情况下预防胰岛素抵抗。在肿瘤坏死因子刺激下抑制炎症介质核因子-kB可能是胰岛素抵抗的预防因素之一。VPP进一步增强了脂肪细胞葡萄糖转运蛋白4(GLUT4)的表达，恢复了肿瘤坏死因子处理的脂肪细胞对葡萄糖的摄取。我们的数据表明，这些多肽在治疗与胰岛素信号受损相关的疾病方面具有潜力。
There is great interest in developing naturally derived compounds, especially bioactive peptides with potential insulin sensitizing effects and/or preventing insulin resistance. Previously, we showed adipogenic and insulin mimetic actions of IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro), the milk-derived tripeptides on cultured preadipocytes, in addition to their previously characterized antihypertensive and anti-inflammatory functions. However, the effect of these peptides on insulin signaling is not known. Therefore, we examined IPP and VPP effects on insulin signaling in preadipocytes, a well-established model for studying insulin signaling. Our results suggested both peptides enhanced insulin signaling and contributed toward the prevention of insulin resistance in the presence of tumor necrosis factor (TNF). Inhibition of inflammatory mediator NF-kB under TNF stimulation was a likely contributor to the prevention of insulin resistance. VPP further enhanced the expression of glucose transporter 4 (GLUT4) in adipocytes and restored glucose uptake in TNF-treated adipocytes. Our data suggested the potential of these peptides in the management of conditions associated with impairments in insulin signaling.