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.

中文翻译：

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牛奶衍生的三肽IPP（Ile-Pro-Pro）和VPP（Val-Pro-Pro）可增强3T3-F442A前脂肪细胞的胰岛素敏感性并防止胰岛素抵抗

开发天然衍生的化合物，特别是具有潜在的胰岛素敏化作用和/或预防胰岛素抵抗的生物活性肽，引起了极大的兴趣。以前，我们显示了IPP（Ile-Pro-Pro）和VPP（Val-Pro-Pro）的脂肪形成和胰岛素模拟作用，这是牛奶中的三肽对培养的前脂肪细胞的作用，此外还具有先前表征的降压和抗炎功能。但是，这些肽对胰岛素信号传导的作用尚不清楚。因此，我们检查了IPP和VPP对前脂肪细胞中胰岛素信号传导的影响，前脂肪细胞是研究胰岛素信号传导的公认模型。我们的结果表明，在存在肿瘤坏死因子（TNF）的情况下，这两种肽均可增强胰岛素信号传导，并有助于预防胰岛素抵抗。在TNF刺激下抑制炎性介质NF-kB可能是预防胰岛素抵抗的原因。VPP进一步增强了脂肪细胞中葡萄糖转运蛋白4（GLUT4）的表达，并恢复了TNF处理的脂肪细胞中的葡萄糖吸收。我们的数据表明这些肽在与胰岛素信号转导障碍相关的疾病管理中的潜力。