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  2. 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

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

  • J Agric Food Chem. 2025 Feb 26;73(8):4659-4672. doi: 10.1021/acs.jafc.4c12559.
Shu Zhang 1 Jingru Sun 1 2 Shibo Yu 1 2 Tianxin Fu 1 Yuchao Feng 3 Zhijiang Li 1 Dongjie Zhang 1 2 4 Changyuan Wang 1 2 5
Affiliations

Affiliations

  • 1 College of Food, Heilongjiang Bayi Agricultural University, Xinfeng Lu 5, Daqing 163319, P. R. China.
  • 2 National Coarse Cereals Engineering Research Center, Daqing 163319, P. R. China.
  • 3 Institute of Quality Standards and Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, P. R. China.
  • 4 Key Laboratory of Agro-Products Processing and Quality Safety of Heilongjiang Province, Daqing 163319, P. R. China.
  • 5 Heilongjiang Food and Biotechnology Innovation and Research Center (International Cooperation), Daqing 163319, P. R. China.
Abstract

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).

Keywords

INS-1 cell; T2DM; active peptides; autophagy; hIAPP.

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