Screening of Chinese giant salamander meat hydrolysates with DPP-Ⅳ inhibitory activity and systematic elucidation of their hypoglycemic functions in mouse model

Shucheng Li^{^a^,^b^,¹}, Changge Guan^{^a^,¹}, Yi Wang^{^a}, Haihong Chen^{^c}, Wei Li^{^c}, Songjun Wang^{^d}, Chong Zhang^{^a^,^b^,^e}, Xinhui Xing^{^a^,^c^,^e^,^f}()

Key Laboratory for Industrial Biocatalysis, Ministry of Education of China, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China

School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 225-8501, Japan

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China

Henan Giant Salamander Protection and Development Association, Luoyang 471000, China

Center for Synthetic and Systems Biology, Tsinghua University, Beijing100084, China

Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518055, China

¹ These authors contributed equally to this work.

Peer review under responsibility of Beijing Academy of Food Sciences.

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Abstract

Type 2 diabetes (T2D) presents a significant health challenge, underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention. This study investigates the potential of proteolytic hydrolysate from artificially cultivated Chinese giant salamander (CGS) meat, a rich protein source, as a preventive strategy for T2D. We produced a CGS meat hydrolysate (CGSh) and demonstrated its ability to inhibit the T2D drug target dipeptidyl peptidase Ⅳ (DPP-Ⅳ) through in vitro assays. We identified 5 peptides (WRPPDH, WAPPSKD, IPDSPF, IPEMIF, and VPIAVPT) with high DPP-Ⅳ inhibitory activity in CGSh, suggesting its potential antidiabetic effects. In vivo experiments showed that CGSh effectively reduced insulin resistance in mice induced with a high-fat diet, as evidenced by a slower increase in blood glucose levels and a decreased HOMA-IR index. 16S rRNA sequencing analysis revealed that CGSh improved gut microbial homeostasis, promoting beneficial microorganisms and reducing harmful bacteria. Metabolomic analyses identified an increase in valeric acid levels and highlighted nine potential biomarker metabolites. By inhibiting metabolic pathways such as AGE-RAGE, CGSh might also prevent diabetic complications and reduce inflammation. These findings suggest that CGSh has a promising hypoglycemic effect, making it a potential functional food ingredient for T2D prevention and treatment.

Keywords

Chinese giant salamander Hypoglycemic effects Bioactive peptides Dipeptidyl dipeptidase Ⅳ Multi-omics analysis

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Y. Misumi, Y. Hayashi, F. Arakawa, et al., Molecular cloning and sequence analysis of human dipeptidyl peptidase Ⅳ, a serine proteinase on the cell surface, Biochim. Biophys. Acta 1131 (1992) 333-336. https://doi.org/10.1016/0167-4781(92)90036-y.