# Dipeptidyl Peptidase-4 Inhibitory Activity of Buckwheat Flour-Derived Peptides and Oral Glucose Tolerance Test of Buckwheat Flour Hydrolysates in Rats

**Authors:** Noe Mitsui, Kouji Shiono, Yoshiya Seto, Tadasu Furusho, Chika Saito, Kosaku Takahashi

PMC · DOI: 10.3390/foods15010092 · Foods · 2025-12-29

## TL;DR

This study identifies two peptides from buckwheat flour that inhibit DPP-4, a target for managing type 2 diabetes, and tests their effect on blood glucose in rats.

## Contribution

The study is the first to identify Ile-Pro-Trp and Ile-Pro-Ile as DPP-4 inhibitory peptides from a plant source.

## Key findings

- Ile-Pro-Trp and Ile-Pro-Leu were identified as DPP-4 inhibitory peptides from buckwheat flour hydrolysates.
- A fraction of buckwheat flour hydrolysate showed a non-significant trend toward reducing blood glucose in a rat OGTT.

## Abstract

Dipeptidyl peptidase-4 (DPP-4) is a protease that degrades incretin and inhibits the secretion of insulin. Consequently, DPP-4 inhibition promotes insulin secretion and prevents the onset of type 2 diabetes. Given the growing interest in food-derived DPP-4 inhibitory peptides as potential functional ingredients, buckwheat (Fagopyrum esculentum) represents a promising source; however, few studies have investigated the bioactivity of peptides derived from buckwheat flour hydrolysates. In this study, two DPP-4 inhibitory peptides, Ile-Pro-Trp and Ile-Pro-Leu, were identified through purification of buckwheat flour hydrolysate and liquid chromatography–tandem mass spectrometry analysis. In a rat oral glucose tolerance test (OGTT), a fraction of buckwheat flour hydrolysate, crudely purified by reverse-phase column chromatography, showed a non-significant trend toward reducing increases in blood glucose. To our knowledge, this study is the first to show that Ile-Pro-Trp isolated from food protein hydrolysates exhibits considerable DPP-4 inhibitory activity. Moreover, this is the first study identifying Ile-Pro-Ile as a DPP-4 inhibitor from a plant source.

## Linked entities

- **Proteins:** DPP4 (dipeptidyl peptidase 4)
- **Diseases:** type 2 diabetes (MONDO:0005148)
- **Species:** Fagopyrum esculentum (taxon 3617)

## Full-text entities

- **Genes:** Dpp4 (dipeptidylpeptidase 4) [NCBI Gene 25253] {aka CD26, DPPIV}
- **Diseases:** type 2 diabetes (MESH:D003924)
- **Chemicals:** Ile-Pro-Leu (-), Glucose (MESH:D005947), Ile-Pro-Ile (MESH:C041445), blood glucose (MESH:D001786)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Fagopyrum esculentum (common buckwheat, species) [taxon 3617]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12785546/full.md

## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785546/full.md

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Source: https://tomesphere.com/paper/PMC12785546