新型乳源肽DAHMP1介导的胰岛细胞功能改善在T1DM治疗中的作用机制研究

DAHMP1 is a human milk-derived peptide without any function report, which with good molecular basis for peptide drugs such as small molecular weight, strong stability and high lipotropy. Previously, we found that DAHMP1 decreases apoptosis of islet cells. Notablely, DAHMP1 could inhibit islet cells apoptosis, promote insulin secretion and reduce the level of blood sugar, indicating that DAHMP1 may play a potential role in T1DM prevention and treatment. It further revealed that its effects were associated with activation of PI3K/Akt signaling pathway. It has been reported that Akt is closely related to the apoptosis of islet cells. This research intends to reveal the consistency of the function of DAHMP1 in different islet cells and in different T1DM animal models and further evaluate its possibility in T1DM prevention and control. Furthermore, we plan to carry out rescue experiments and Pull-down experiments to elucidate the molecular mechanism of DAHMP1. This research may provide a new opportunity for T1DM prevention and treatment.

DAHMP1是一条来源于母乳的未知功能小肽，具有分子量低、稳定性高、亲脂性好等作为多肽药物的良好分子基础。前期发现，DAHMP1可抵抗炎症因子引发的胰岛细胞凋亡，动物实验研究证实DAHMP1具有抵抗STZ诱导的胰岛细胞凋亡、上调胰岛素水平、降低血糖的作用，展示出1型糖尿病（Type 1 diabetes mellitus，T1DM）治疗的潜质；进一步研究发现DAHMP1与PI3K/Akt信号通路中Akt蛋白磷酸化水平有关，已证实Akt与小鼠胰岛细胞凋亡密切相关。本研究拟通过评估DAHMP1在不同胰岛细胞、不同T1DM动物模型中的功能一致性，论证DAHMP1作为T1DM防治手段的可能性；通过挽救实验、Pull-down等方法，深入阐明DAHMP1作用的分子机制。研究有望为T1DM的预防和治疗提供新手段。

生物活性肽因参与多种生命过程而收到越来越多的关注。DAHMP1是一条既往尚无功能报道的乳源性多肽。在本研究中，我们发现DAHMP1可抵抗炎症因子诱导引发的胰岛β细胞凋亡；进一步研究表明DAHMP1具有抑制胰岛β细胞凋亡、促进胰岛素分泌进而降低血糖的作用。此外，DAHMP1还可以上调HIF-1α 和 p-Akt的水平，提示DAHMP1与PI3K/Akt/ HIF-1α信号通路的激活有关。综上，DAHMP1有望为T1DM的发病机制和临床治疗提供了一个新的视角。