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Bee pollen-derived peptide with dual DPP-IV Inhibition and glucose transport modulation
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  • Published: 06 February 2026

Bee pollen-derived peptide with dual DPP-IV Inhibition and glucose transport modulation

  • Usa Mongkolnkrajang1,
  • Kittisak Kuptawach1,
  • Papassara Sangtanoo2,
  • Tanatorn Saisavoey2,
  • Patamalai Boonserm2,
  • Onrapak Reamtong3,
  • Piroonporn Srimongkol4 &
  • …
  • Aphichart Karnchanatat2,4 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Bioinformatics
  • Diabetes
  • Enzymes
  • Mass spectrometry
  • Nutrition
  • Peptides
  • Proteases

Abstract

This study investigates the potential of bee pollen protein hydrolysate (BPPH) as a natural source of bioactive peptides capable of inhibiting dipeptidyl peptidase IV (DPP-IV) for the management of type 2 diabetes mellitus (T2DM), a metabolic disorder characterized by insulin resistance and hyperglycemia. BPPH was generated through pepsin–pancreatin digestion, followed by ultrafiltration and RP-HPLC purification. LC-Q-TOF-MS/MS analysis identified Ala-Thr-His-Ala-Leu-Leu-Ala (ATHALLA, AA-7) as a predominant peptide associated with DPP-IV inhibitory activity. AA-7 exhibited strong DPP-IV inhibitory activity (IC50 = 52.63 ± 2.32 µM) relative to the reference inhibitor diprotin A (IC50 = 22.4 ± 1.29 µM). Molecular docking predicted stable binding of AA-7 within the DPP-IV catalytic pocket, mediated by hydrogen bonding and hydrophobic interactions with key residues. AA-7 also modulated glucose uptake in Caco-2 cells, influencing SGLT1 and GLUT2 gene expression in a dose-dependent manner. Docking analysis suggested potential interactions with selected SGLT1 and GLUT2 residues, providing structural support for the observed cellular responses rather than definitive mechanistic evidence. In silico ADMET analysis indicated poor passive membrane permeability and limited predicted intestinal absorption, along with minimal CYP450 interactions and low predicted toxicity, highlighting potential pharmacokinetic limitations while supporting a favorable safety profile. These findings highlight AA-7 as a dual-action peptide with demonstrated DPP-IV inhibitory activity and the ability to modulate glucose transport in vitro, supporting the potential of bee-pollen-derived peptides for glycemic regulation and functional food or nutraceutical applications.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary material. Raw data that support the findings of this study are available from the corresponding author, upon reasonable request.

References

  1. Galicia-Garcia, U. et al. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci. 21, 6275. https://doi.org/10.3390/ijms21176275 (2020).

    Google Scholar 

  2. Ogurtsova, K. et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res. Clin. Pract. 218, 40–50. https://doi.org/10.1016/j.diabres.2017.03.024 (2017).

    Google Scholar 

  3. Wu, Y., Ding, Y., Tanaka, Y. & Zhang, W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int. J. Med. Sci. 11, 1185–1200. https://doi.org/10.7150/ijms.10001 (2014).

    Google Scholar 

  4. Li, Y. et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies, signal transduct. Target. Ther. 8, 152. https://doi.org/10.1038/s41392-023-01400-z (2023).

    Google Scholar 

  5. Ahrén, B. & Schmitz, O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm. Metab. Res. 36, 867–876. https://doi.org/10.1055/s-2004-826178 (2004).

    Google Scholar 

  6. Barnett, A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int. J. Clin. Pract. 60, 1454–1470. https://doi.org/10.1111/j.1742-1241.2006.01178.x (2006).

    Google Scholar 

  7. Derosa, G. & Maffioli, P. Dipeptidyl peptidase-4 inhibitors: 3 years of experience. Diabetes Technol. Ther. 14, 350–364. https://doi.org/10.1089/dia.2011.0204 (2012).

    Google Scholar 

  8. Saini, K., Sharma, S. & Khan, Y. DPP-4 inhibitors for treating T2DM - hype or hope? An Analysis based on the current literature. Front. Mol. Biosci. 10, 1130625. https://doi.org/10.3389/fmolb.2023.1130625 (2023).

    Google Scholar 

  9. Li, N. et al. Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus. Eur. J. Med. Chem. 151, 145–157. https://doi.org/10.1016/j.ejmech.2018.03.041 (2018).

    Google Scholar 

  10. Martini, S., Cattivelli, A., Conte, A. & Tagliazucchi, D. Application of a combined peptidomics and in Silico approach for the identification of novel dipeptidyl peptidase-IV-inhibitory peptides in in vitro digested Pinto bean protein extract. Curr. Issues Mol. Biol. 44, 139–151. https://doi.org/10.3390/cimb44010011 (2021).

    Google Scholar 

  11. Amigo, L. & Hernández-Ledesma, B. Current evidence on the bioavailability of food bioactive peptides. Molecules 25, 4479. https://doi.org/10.3390/molecules25194479 (2020).

    Google Scholar 

  12. Yu, J., Chen, G., Jin, Y., Zhang, M. & Wu, T. Research progress of bioactive peptides in improving type II diabetes. Foods 14, 340. https://doi.org/10.3390/foods14030340 (2025).

    Google Scholar 

  13. Gao, J., Gong, H. & Mao, X. Dipeptidyl peptidase-IV inhibitory activity and related molecular mechanism of bovine α-lactalbumin-derived peptides. Molecules 25, 3009. https://doi.org/10.3390/molecules25133009 (2020).

    Google Scholar 

  14. Zhang, Y. et al. Comparison of dipeptidyl peptidase IV-inhibitory activity of peptides from bovine and caprine milk casein by in Silico and in vitro analyses. Int. Dairy. J. 53, 37–44. https://doi.org/10.1016/j.idairyj.2015.10.001 (2016).

    Google Scholar 

  15. Xu, F. et al. Identification and quantification of DPP-IV-inhibitory peptides from hydrolyzed-rapeseed-protein-derived Napin with analysis of the interactions between key residues and protein domains. J. Agric. Food Chem. 67, 3679–3690. https://doi.org/10.1021/acs.jafc.9b01069 (2019).

    Google Scholar 

  16. Zhang, Y. et al. Dipeptidyl peptidase IV-inhibitory peptides derived from silver carp (Hypophthalmichthys molitrix Val.) proteins. J. Agric. Food Chem. 64, 831–839. https://doi.org/10.1021/acs.jafc.5b05429 (2016).

    Google Scholar 

  17. Mu, X., Wang, R., Cheng, C., Ma, Y. & Li, Q. Two novel peptides derived from oat with inhibitory activity against dipeptidyl peptidase-IV: the related mechanism revealed by molecular Docking and in vitro and in situ effects. J. Food Meas. Char. 18, 3087–3099. https://doi.org/10.1007/s11694-024-02387-z (2024).

    Google Scholar 

  18. Wu, W. et al. Exploring dipeptidyl peptidase-IV inhibitory peptides from Tartary buckwheat protein: A study of hydrolysis, fractionation, and molecular interactions. J. Food Sci. 89, 9108–9119. https://doi.org/10.1111/1750-3841.17525 (2024).

    Google Scholar 

  19. Santos-Hernández, M., Cermeño, M., Recio, I. & FitzGerald, R. J. Vitro dipeptidyl peptidase IV inhibitory activity and in situ insulinotropic activity of milk and egg white protein digests. Food Funct. 12, 12372–12380. https://doi.org/10.1039/d1fo00641j (2021).

    Google Scholar 

  20. Velarde-Salcedo, A. J. et al. In vitro Inhibition of dipeptidyl peptidase IV by peptides derived from the hydrolysis of Amaranth (Amaranthus hypochondriacus L.) proteins. Food Chem. 136, 758–764. https://doi.org/10.1016/j.foodchem.2012.08.032 (2013).

    Google Scholar 

  21. Caron, J., Domenger, D., Dhulster, P., Ravallec, R. & Cudennec, B. Using Caco-2 cells as novel identification tool for food-derived DPP-IV inhibitors. Food Res. Int. 92, 113–118. https://doi.org/10.1016/j.foodres.2017.01.002 (2017).

    Google Scholar 

  22. Thakur, M. & Nanda, V. Composition and functionality of bee pollen: A review. Trends Food Sci. Technol. 98, 82–106. https://doi.org/10.1016/j.tifs.2020.02.001 (2020).

    Google Scholar 

  23. El Ghouizi, A. et al. Bee pollen as functional food: insights into its composition and therapeutic properties. Antioxidants 12, 557. https://doi.org/10.3390/antiox12030557 (2023).

    Google Scholar 

  24. Ilie, C. L. et al. Bee pollen extracts: chemical composition, antioxidant properties, and effect on the growth of selected probiotic and pathogenic bacteria. Antioxidants 11, 959. https://doi.org/10.3390/antiox11050959 (2022).

    Google Scholar 

  25. Saisavoey, T., Sangtanoo, P., Chanchao, C., Reamtong, O. & Karnchanatat, A. Identification of novel anti-inflammatory peptides from bee pollen (Apis mellifera) hydrolysate in lipopolysaccharide-stimulated RAW264.7 macrophages. J. Apic. Res. 60, 280–289. https://doi.org/10.1080/00218839.2020.1745434 (2020).

    Google Scholar 

  26. Saisavoey, T., Sangtanoo, P., Srimongkol, P., Reamtong, O. & Karnchanatat, A. Hydrolysates from bee pollen could induced apoptosis in human bronchogenic carcinoma cells (ChaGo-K-1). J. Food Sci. Technol. 58, 752–763. https://doi.org/10.1007/s13197-020-04592-2 (2021).

    Google Scholar 

  27. Khongkarat, P., Traiyasut, P., Phuwapraisirisan, P. & Chanchao, C. First report of fatty acids in Mimosa Diplotricha bee pollen with in vitro lipase inhibitory activity. PeerJ 10, e12722. https://doi.org/10.7717/peerj.12722 (2022).

    Google Scholar 

  28. Aursuwanna, T. et al. Investigating the cellular antioxidant and anti-inflammatory effects of the novel peptides in Lingzhi mushrooms. Heliyon 8, e11067. https://doi.org/10.1016/j.heliyon.2022.e11067 (2022).

    Google Scholar 

  29. Sangtanoo, P. et al. Bee pollen peptides as potent tyrosinase inhibitors with anti-melanogenesis effects in murine b16f10 melanoma cells and zebrafish embryos. Sci. Rep. 14, 30834. https://doi.org/10.1038/s41598-024-81495-8 (2024).

    Google Scholar 

  30. Boonmee, A., Srisomsap, C., Karnchanatat, A. & Sangvanich, P. An antioxidant protein in Curcuma Comosa Roxb. Rhizomes. Food Chem. 124, 476–480. https://doi.org/10.1016/j.foodchem.2010.06.057 (2011).

    Google Scholar 

  31. Kamal, H. et al. Inhibitory properties of camel Whey protein hydrolysates toward liver cancer cells, dipeptidyl peptidase-IV, and inflammation. J. Dairy. Sci. 101, 8711–8720. https://doi.org/10.3168/jds.2018-14586 (2018).

    Google Scholar 

  32. Xiong, G. et al. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 49, W5–W14. https://doi.org/10.1093/nar/gkab255 (2021).

    Google Scholar 

  33. Xu, F. et al. Absorption and metabolism of peptide WDHHAPQLR derived from rapeseed protein and Inhibition of HUVEC apoptosis under oxidative stress. J. Agric. Food Chem. 66, 5178–5189. https://doi.org/10.1021/acs.jafc.8b01620 (2018).

    Google Scholar 

  34. Livak, K. J. & Schmittgen, T. D. T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method, Methods 25 (2001) 402–408. (2001). https://doi.org/10.1006/meth.2001.1262

  35. Yan, Z. et al. Gastrointestinal digestion of food proteins: Anticancer, antihypertensive, anti-obesity, and Immunomodulatory mechanisms of the derived peptides. Food Res. Int. 189, 114573. https://doi.org/10.1016/j.foodres.2024.114573 (2024).

    Google Scholar 

  36. Montoya-Rodríguez, A., Milán-Carrillo, J., Dia, V. P. & Reyes-Moreno, C. González de Mejía, Pepsin-pancreatin protein hydrolysates from extruded Amaranth inhibit markers of atherosclerosis in LPS-induced THP-1 macrophages-like human cells by reducing expression of proteins in LOX-1 signaling pathway. Proteome Sci. 12, 30. https://doi.org/10.1186/1477-5956-12-30 (2014).

    Google Scholar 

  37. Lacroix, I. M. E. & Li-Chan, E. C. Y. Isolation and characterization of peptides with dipeptidyl peptidase-IV inhibitory activity from pepsin-treated bovine Whey proteins. Peptides 54, 39–48. https://doi.org/10.1016/j.peptides.2014.01.002 (2014).

    Google Scholar 

  38. Lacroix, I. M. E. & Li-Chan, E. C. Y. Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int. Dairy. J. 25, 97–102. https://doi.org/10.1016/j.idairyj.2012.01.003 (2012).

    Google Scholar 

  39. Mojica, L., Chen, K. & de Mejía, E. G. Impact of commercial precooking of common bean (Phaseolus vulgaris) on the generation of peptides, after pepsin-pancreatin hydrolysis, capable to inhibit dipeptidyl peptidase-IV. J. Food Sci. 80, H188–H198. https://doi.org/10.1111/1750-3841.12726 (2015).

    Google Scholar 

  40. Chandrasekaran, S., Luna-Vital, D. & de Mejia, E. G. Identification and comparison of peptides from Chickpea protein hydrolysates using either Bromelain or Gastrointestinal enzymes and their relationship with markers of type 2 diabetes and bitterness. Nutrients 12, 3843. https://doi.org/10.3390/nu12123843 (2020).

    Google Scholar 

  41. You, H. et al. Preparation and identification of dipeptidyl peptidase IV inhibitory peptides from Quinoa protein. Food Res. Int. 156, 1–9. https://doi.org/10.1016/j.foodres.2022.111176 (2022).

    Google Scholar 

  42. Ding, L. et al. Identification and characterization of dipeptidyl peptidase IV inhibitory peptides from wheat gluten proteins. J. Cereal Sci. 103, 1–7. https://doi.org/10.1016/j.jcs.2021.103396 (2022).

    Google Scholar 

  43. Kumar, A., Kumar, M. H. S., Rajani, C. S., Sabikhi, L. & Naik, N. L. Dipeptidyl peptidase-IV inhibitory potential of alpha-lactalbumin extracted from milk of Gir cows: A Bos indicus species. Int. J. Dairy. Technol. 75, 527–537. https://doi.org/10.1111/1471-0307.12868 (2022).

    Google Scholar 

  44. González-Montoya, M., Hernández-Ledesma, B., Mora-Escobedo, R. & Martínez-Villaluenga, C. Bioactive peptides from germinated soybean with anti-diabetic potential by Inhibition of dipeptidyl peptidase-IV, α-amylase, and α-glucosidase enzymes. Int. J. Mol. Sci. 19, 2883. https://doi.org/10.3390/ijms19102883 (2018).

    Google Scholar 

  45. Wang, B., Xie, N. & Li, B. Influence of peptide characteristics on their stability, intestinal transport, and in vitro bioavailability: A review. J. Food Biochem. 43, 1–6. https://doi.org/10.1111/jfbc.12571 (2019).

    Google Scholar 

  46. Agustia, F. C., Supriyadi, A., Murdiati, R. & Indrati Formation of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from Jack bean (Canavalia ensiformis (L.) DC.) sprout in simulated digestion. Food Sci. Biotechnol. 33, 645–655. https://doi.org/10.1007/s10068-023-01343-9 (2023).

    Google Scholar 

  47. Liu, R., Cheng, J. & Wu, H. Discovery of food-derived dipeptidyl peptidase IV inhibitory peptides: A review. Int. J. Mol. Sci. 20, 463. https://doi.org/10.3390/ijms20030463 (2019).

    Google Scholar 

  48. Ojeda-Montes, M. J. et al. Activity and selectivity cliffs for DPP-IV inhibitors: lessons we can learn from SAR studies and their application to virtual screening. Med. Res. Rev. 38, 1874–1915. https://doi.org/10.1002/med.21499 (2018).

    Google Scholar 

  49. Matuszewska, E. et al. Mass spectrometry-based identification of bioactive bee pollen proteins: evaluation of allergy risk after bee pollen supplementation. Molecules 27, 7733. https://doi.org/10.3390/molecules27227733 (2022).

    Google Scholar 

  50. Kacemi, R. & Campos, M. G. Translational research on bee pollen as a source of nutrients: A scoping review from bench to real world. Nutrients 15, 2413. https://doi.org/10.3390/nu15102413 (2023).

    Google Scholar 

  51. Nongonierma, A. B. & FitzGerald, R. J. Strategies for the discovery and identification of food protein-derived biologically active peptides. Trends Food Sci. Technol. 69, 289e305. https://doi.org/10.1016/j.tifs.2017.03.003 (2017).

    Google Scholar 

  52. Cermeño, M. et al. Peptide identification from a Porphyra dioica protein hydrolysate with antioxidant, angiotensin converting enzyme and dipeptidyl peptidase IV inhibitory activities. Food Funct. 10, 3421–3429. https://doi.org/10.1039/c9fo00680j (2019).

    Google Scholar 

  53. Wang, W. et al. Identification and characterization of dipeptidyl peptidase-IV inhibitory peptides from oat proteins. Foods 11, 1406. https://doi.org/10.3390/foods11101406 (2022).

    Google Scholar 

  54. Zhang, A., Wang, K., Liu, X. & Zhang, X. Isolation and identification of dipeptidyl peptidase-IV inhibitory peptides from Sacha Inchi meal. J. Sci. Food Agric. 103, 2926–2938. https://doi.org/10.1002/jsfa.12464 (2023).

    Google Scholar 

  55. Nongonierma, A. B. et al. Dipeptidyl peptidase IV (DPP-IV) inhibitory properties of a camel Whey protein enriched hydrolysate Preparation. Food Chem. 279, 70–79. https://doi.org/10.1016/j.foodchem.2018.11.142 (2019).

    Google Scholar 

  56. Lin, Y. S., Han, C. H., Lin, S. Y. & Hou, W. C. Synthesized peptides from Yam Dioscorin hydrolysis in Silico exhibit dipeptidyl peptidase-IV inhibitory activities and oral glucose tolerance improvements in normal mice. J. Agric. Food Chem. 64, 6451–6458. https://doi.org/10.1021/acs.jafc.6b02403 (2016).

    Google Scholar 

  57. Jin, R., Teng, X., Shang, J., Wang, D. & Liu, N. Identification of novel DPP-IV inhibitory peptides from Atlantic salmon (Salmo salar) skin. Food Res. Int. 133, 109161. https://doi.org/10.1016/j.foodres.2020.109161 (2020).

    Google Scholar 

  58. Nongonierma, A. B., Lalmahomed, M., Paolella, S. & FitzGerald, R. J. Milk protein isolate (MPI) as a source of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Chem. 231, 202–211. https://doi.org/10.1016/j.foodchem.2017.03.123 (2017).

    Google Scholar 

  59. Power, O., Fernandez, A., Norris, R. & Riera, F. A. Selective enrichment of bioactive properties during ultrafiltration of a tryptic digest of beta-lactoglobulin. J. Funct. Foods. 9, 38–47. https://doi.org/10.1016/j.jff.2014.04.002 (2014).

    Google Scholar 

  60. Ji, W., Zhang, C. & Ji, H. Two novel bioactive peptides from Antarctic Krill with dual angiotensin converting enzyme and dipeptidyl peptidase IV inhibitory activities. J. Food Sci. 82, 1742–1749. https://doi.org/10.1111/1750-3841.13735 (2017).

    Google Scholar 

  61. Rivero-Pino, F., Guadix, A. & Guadix, E. M. Identification of novel dipeptidyl peptidase IV and α-glucosidase inhibitory peptides from Tenebrio molitor. Food Funct. 12, 873–880. https://doi.org/10.1039/d0fo02696d (2021).

    Google Scholar 

  62. Zhang, M. et al. Food-derived dipeptidyl peptidase IV inhibitory peptides: Production, identification, structure-activity relationship, and their potential role in glycemic regulation. Crit. Rev. Food Sci. Nutr. 64, 2053–2075. https://doi.org/10.1080/10408398.2022.2120454 (2024).

    Google Scholar 

  63. Chen, Z. et al. The discovery and characterization of a potent DPP-IV inhibitory peptide from oysters for the treatment of type 2 diabetes based on computational and experimental studies. Mar. Drugs. 22, 361. https://doi.org/10.3390/md22080361 (2024).

    Google Scholar 

  64. Rodhi, A. M., Yap, P. G., Abayomi, O. O. & Gan, C. Y. A review on the types of amino acid at ultimate, penultimate and antepenultimate position in some dipeptidyl-peptidase IV inhibitory peptides based on molecular Docking analysis. Food Chem. Adv. 2, 100244. https://doi.org/10.1016/j.focha.2023.100244 (2023).

    Google Scholar 

  65. Wang, L. et al. Therapeutic peptides: current applications and future directions, signal transduct. Target. Ther. 7, 48. https://doi.org/10.1038/s41392-022-00904-4 (2022).

    Google Scholar 

  66. Song, T., Lv, M., Sun, B., Zheng, L. & Zhao, M. Tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) regulate the proliferation and migration of vascular smooth muscle cells by interfering Ang II-induced human umbilical vein endothelial cells derived EVs delivering RNAs to VSMCs in the co-culture model. J. Agric. Food Chem. 68, 6628–6637. https://doi.org/10.1021/acs.jafc.0c02060 (2020).

    Google Scholar 

  67. Chakrabarti, S., Guha, S. & Majumder, K. Food-derived bioactive peptides in human health: challenges and opportunities. Nutrients 10, 1738. https://doi.org/10.3390/nu10111738 (2018).

    Google Scholar 

  68. He, R. et al. Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin-angiotensin system pathway in spontaneously hypertensive rat. NPJ Sci. Food. 3, 1. https://doi.org/10.1038/s41538-018-0033-5 (2019).

    Google Scholar 

  69. Mehrdadi, S. Lipid-based nanoparticles as oral drug delivery systems: overcoming poor Gastrointestinal absorption and enhancing bioavailability of peptide and protein therapeutics. Adv. Pharm. Bull. 14, 48–66. https://doi.org/10.34172/apb.2024.016 (2024).

    Google Scholar 

  70. Renukuntla, J., Vadlapudi, A. D., Patel, A., Boddu, S. H. & Mitra, A. K. Approaches for enhancing oral bioavailability of peptides and proteins. Int. J. Pharm. 447, 75–93. https://doi.org/10.1016/j.ijpharm.2013.02.030 (2013).

    Google Scholar 

  71. Arranz, E. et al. Dairy and plant based protein beverages: in vitro digestion behaviour and effect on intestinal barrier biomarkers. Food Res. Int. 169, 112815. https://doi.org/10.1016/j.foodres.2023.112815 (2023).

    Google Scholar 

  72. Khavinson, V., Linkova, N., Kozhevnikova, E., Dyatlova, A. & Petukhov, M. Transport of biologically active ultrashort peptides using POT and LAT carriers. Int. J. Mol. Sci. 23, 7733. https://doi.org/10.3390/ijms23147733 (2022).

    Google Scholar 

  73. Mathur, V. et al. Insight into structure activity relationship of DPP-4 inhibitors for development of antidiabetic agents. Molecules 28, 5860. https://doi.org/10.3390/molecules28155860 (2023).

    Google Scholar 

  74. Gu, H. et al. Dipeptidyl peptidase-IV inhibitory activity of millet protein peptides and the related mechanisms revealed by molecular Docking. LWT 138, 110587. https://doi.org/10.1016/j.lwt.2020.11058 (2021).

    Google Scholar 

  75. Li, Y., Zhang, F., Gong, J. & Peng, C. Two novel dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides identified from truffle (Tuber sinense) by peptidomics, in silico, and molecular Docking analysis. J. Food Compos. Anal. 121, 105384. https://doi.org/10.1016/j.jfca.2023.105384 (2023).

    Google Scholar 

  76. Zan, R. et al. Identification of novel dipeptidyl peptidase-IV inhibitory peptides in Chickpea protein hydrolysates. J. Agric. Food Chem. 71, 8211–8219. https://doi.org/10.1021/acs.jafc.3c00603 (2023).

    Google Scholar 

  77. Zhang, M. et al. Rapid screening of novel dipeptidyl peptidase-4 inhibitory peptides from pea (Pisum sativum L.) protein using peptidomics and molecular Docking. J. Agric. Food Chem. 70, 10221–10228. https://doi.org/10.1021/acs.jafc.2c03949 (2022).

    Google Scholar 

  78. Zhang, S. et al. DPP-IV inhibitory peptides from Coix seed prolamins: Release, identification, and analysis of the interaction between key residues and enzyme domains. J. Agric. Food Chem. 71, 14575–14592. https://doi.org/10.1021/acs.jafc.3c02733 (2023).

    Google Scholar 

  79. Wu, W. et al. Identification and characterization of two novel dipeptidyl peptidase-IV inhibitory peptides from the simulated Gastrointestinal digestion of Tartary buckwheat proteins. Food Chem. 473, 143067. https://doi.org/10.1016/j.foodchem.2025.143067 (2025).

    Google Scholar 

  80. Li, J. et al. Screening, identification, and mechanistic exploration of DPP-IV inhibitory peptides from collagen in Esox Lucius skin. Food Biosci. 63, 105698. https://doi.org/10.1016/j.fbio.2024.105698 (2025).

    Google Scholar 

  81. Hu, H. et al. Identification and molecular mechanism of a novel DPP-IV inhibitory tetrapeptide IPVK from rabbit meat proteins: insights from in Silico study and experimental validation. Food Biosci. 63, 105766. https://doi.org/10.1016/j.fbio.2024.105766 (2025).

    Google Scholar 

  82. Xie, Y. et al. Preparation, characterization, and mechanism of DPP-IV inhibitory peptides derived from bactrian camel milk. Int. J. Biol. Macromol. 277 (Pt 3), 134232. https://doi.org/10.1016/j.ijbiomac.2024.134232 (2024).

    Google Scholar 

  83. Dang, K. et al. Screening and evaluation of novel DPP-IV inhibitory peptides in goat milk based on molecular Docking and molecular dynamics simulation. Food Chem. X. 25, 102217. https://doi.org/10.1016/j.fochx.2025.102217 (2025).

    Google Scholar 

  84. Mu, X. et al. Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro. Curr. Res. Food Sci. 9, 100893. https://doi.org/10.1016/j.crfs.2024.100893 (2024).

    Google Scholar 

  85. Mojica, L., Luna-Vital, D. A., Gonzalez de, E. & Mejia Black bean peptides inhibit glucose uptake in Caco-2 adenocarcinoma cells by blocking the expression and translocation pathway of glucose transporters. Toxicol. Rep. 5, 552–560. https://doi.org/10.1016/j.toxrep.2018.04.007 (2018).

    Google Scholar 

  86. Lammi, C. et al. Soybean- and lupin-derived peptides inhibit DPP-IV activity on in situ human intestinal Caco-2 cells and ex vivo human serum. Nutrients 10, 1082. https://doi.org/10.3390/nu10081082 (2018).

    Google Scholar 

  87. Alzaid, F., Cheung, H. M., Preedy, V. R. & Sharp, P. A. Regulation of glucose transporter expression in human intestinal Caco-2 cells following exposure to an anthocyanin-rich berry extract. PLoS One. 8, e78932. https://doi.org/10.1371/journal.pone.0078932 (2013).

    Google Scholar 

  88. Johnston, K., Sharp, P., Clifford, M. & Morgan, L. Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells. FEBS Lett. 579, 1653–1657. https://doi.org/10.1016/j.febslet.2004.12.099 (2005).

    Google Scholar 

  89. Kwon, O. et al. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J. 21, 366–377. https://doi.org/10.1096/fj.06-6620com (2007).

    Google Scholar 

  90. Vernaleken, A. et al. Tripeptides of RS1 (RSC1A1) inhibit a monosaccharide-dependent exocytotic pathway of Na+-D-glucose cotransporter SGLT1 with high affinity. J. Biol. Chem. 282, 28501–28513. https://doi.org/10.1074/jbc.M705416200 (2007).

    Google Scholar 

  91. Dugardin, C. et al. An exploratory study of the role of dietary proteins in the regulation of intestinal glucose absorption. Front. Nutr. 8, 769773. https://doi.org/10.3389/fnut.2021.769773 (2022).

    Google Scholar 

  92. Hiramatsu, H. et al. The crystal structure of human dipeptidyl peptidase IV (DPPIV) complex with Diprotin A. Biol. Chem. 385, 561–564. https://doi.org/10.1515/BC.2004.068 (2004).

    Google Scholar 

  93. Thoma, R. et al. Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV. Structure 11, 947–959. https://doi.org/10.1016/s0969-2126(03)00160-6 (2003).

    Google Scholar 

  94. Watanabe, A. et al. The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature 468, 988–991. https://doi.org/10.1038/nature09580 (2010).

    Google Scholar 

  95. Deng, D. et al. Molecular basis of ligand recognition and transport by glucose transporters. Nature 526, 391–396. https://doi.org/10.1038/nature14655 (2015).

    Google Scholar 

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Acknowledgements

The authors wish to express their gratitude to the Institute of Biotechnology and Genetic Engineering at Chulalongkorn University for the use of the facilities which were necessary in order to complete this research study.

Funding

The authors wish to express their sincere gratitude to the 90th Anniversary of Chulalongkorn University Fund, Thailand (Ratchadaphiseksomphot Endowment Fund; GCUGR1125642023M), as well as and the Thailand Science Research and Innovation Fund Chulalongkorn University (BCG_FF_69_038_6100_002). for their financial assistance, without which the completion of this study would not have been feasible.

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Authors and Affiliations

  1. Program in Biotechnology, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok, 10330, Thailand

    Usa Mongkolnkrajang & Kittisak Kuptawach

  2. Center of Excellence in Bioconversion and Bioseparation for Platform Chemical Production, The Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok, 10330, Thailand

    Papassara Sangtanoo, Tanatorn Saisavoey, Patamalai Boonserm & Aphichart Karnchanatat

  3. Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand

    Onrapak Reamtong

  4. High-Value Food from Mushrooms and Bioactive Plants in the Green Economy Value Chain Research Group, The Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok, 10330, Thailand

    Piroonporn Srimongkol & Aphichart Karnchanatat

Authors
  1. Usa Mongkolnkrajang
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Contributions

Conceptualization: U.M., A.K.; Data curation: U.M.; Formal analysis: U.M.; Funding acquisition: A.K.; Investigation: A.K.; Methodology: U.M., K.K., P.S., T.S., P.B., O.R., P.Sr.; Project administration: A.K.; Resources: U.M., A.K.; Software: U.M., P.B., O.R., P.Sr.; Supervision: A.K.; Validation: U.M.; Visualization: U.M., O.R.; Writing – original draft: U.M., A.K.; Writing – review & editing: U.M., A.K.

Corresponding author

Correspondence to Aphichart Karnchanatat.

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All methods were carried out in accordance with relevant guidelines and regulations. Plant experimental research, including the collection of plant material, complied with institutional, national, and international standards.

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Mongkolnkrajang, U., Kuptawach, K., Sangtanoo, P. et al. Bee pollen-derived peptide with dual DPP-IV Inhibition and glucose transport modulation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39009-1

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  • Received: 16 May 2025

  • Accepted: 02 February 2026

  • Published: 06 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-39009-1

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Keywords

  • Bee pollen
  • Bioactive peptide
  • DPP-IV inhibitor
  • Glucose uptake
  • GLUT2
  • SGLT1
  • Type 2 diabetes mellitus
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