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Molecular Observations on the Regulation of hIAPP Aggregation Process and Enhancement of Autophagy by the Short Peptide LPFYPN and Its Modified Peptides of Coix Seed Prolamins

文献类型： 外文期刊

作者： Zhang, Shu 1 ; Sun, Jingru 1 ; Yu, Shibo 1 ; Fu, Tianxin 1 ; Feng, Yuchao 3 ; Li, Zhijiang 1 ; Zhang, Dongjie 1 ; Wang, Changyuan 1 ;

作者机构： 1.Heilongjiang Bayi Agr Univ, Coll Food, Daqing 163319, Peoples R China

2.Natl Coarse Cereals Engn Res Ctr, Daqing 163319, Peoples R China

3.Chinese Acad Agr Sci, Inst Qual Stand & Testing Technol Agroprod, Beijing 100081, Peoples R China

4.Key Lab Agroprod Proc & Qual Safety Heilongjiang P, Daqing 163319, Peoples R China

5.Heilongjiang Food & Biotechnol Innovat & Res Ctr I, Daqing 163319, Peoples R China

关键词： hIAPP; active peptides; autophagy; T2DM; INS-1 cell

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.2； 五年影响因子：6.4 ）

ISSN： 0021-8561

年卷期： 2025 年 73 卷 8 期

页码：

收录情况： SCI

摘要： Inhibiting the fibrotic aggregation of the human islet amyloid polypeptide (hIAPP) and accelerating aggregate clearance are crucial factors in type II diabetes regulation. Autophagy plays a central role in hIAPP fibrotic degradation. We investigated how the coix seed prolamin-derived active peptide (LPFYPN, LP6) and its modifying peptides affect hIAPP aggregation and autophagic processes in induced rat insulinoma (INS-1) cells. Both LP6 and its modified peptides inhibited the fibrotic aggregation of hIAPP, an effect related to the binding site within the core region of hIAPP. Additionally, LP6 and the modified peptides reduced hIAPP-induced cytotoxicity, enhanced LC3-II/LC3-I, decreased p62 protein levels, and promoted autophagy by inhibiting the PI3K-Akt-mTOR signaling pathway, thereby upregulating ULK-1 and Beclin-1 expression. Finally, LP6 modified with selenium showed superior inhibition of hIAPP aggregation and cytotoxicity as well as regulation of autophagic flow. These findings emphasize the potential of LP6 and its modified peptides in regulating type II diabetes and other amyloid-related diseases and indicate that they could be further developed as novel functional food ingredients against type 2 diabetes mellitus (T2DM).

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