Bioactive peptides from purified and digested adzuki bean (Vigna angularis) β-vignin on type-2 diabetes-related pathways: effect and mechanism of action in a liver model under healthy and insulin-resistant states

Kwan, Shu Hang

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https://hdl.handle.net/2142/130151 Copy

Description

Title

Bioactive peptides from purified and digested adzuki bean (Vigna angularis) β-vignin on type-2 diabetes-related pathways: effect and mechanism of action in a liver model under healthy and insulin-resistant states

Author(s)

Kwan, Shu Hang

Issue Date

2025-07-10

Director of Research (if dissertation) or Advisor (if thesis)

Gonzalez de Mejia, Elvira

Doctoral Committee Chair(s)

Madak-Erdogan, Zeynep

Committee Member(s)

• Amengual, Jaume
• Ridlon, Jason M

Department of Study

Nutritional Sciences

Discipline

Nutritional Sciences

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Adzuki bean β-vignin
• Antidiabetic potential
• Dipeptidyl peptidase IV inhibition
• Glucose uptake
• Insulin resistance
• Vigna angularis

Abstract

Diabetes is one of the four major types of noncommunicable diseases in the world, and it is projected to affect 68.1 million individuals in the U.S. by 2050. Thus, there is a need for a low-cost antidiabetic food ingredient. Adzuki beans were found to have antidiabetic properties and were long used to manage type 2 diabetes (T2D). However, there is limited research investigating the antidiabetic potential of adzuki beans. In particular, no one has investigated the potential of adzuki bean β-vignin protein and its peptides in modulating the T2D-related markers. This research had two aims. Aim 1 identified the functional peptides produced from digesting β-vignin protein and characterized the chemical and biological properties of these peptides, in comparison to those from soybean β-conglycinin. LC-QTOF-MS/MS peptide sequencing identified Val-Pro (VP), Pro-Met (PM), Phe-Asn-Glu (FNE) (molecular weights ranging from 214-741 Da) from the colonic digests, with an adzuki bean β-vignin precursor. BIOPEP-UWM database showed that these peptides exhibited bioactivity as dipeptidyl peptidase IV (DPP IV) inhibitors. The identified adzuki bean β-vignin-derived peptides could bind to the DPP IV enzyme at the same binding site as linagliptin, an FDA-approved diabetic medication, suggesting the antidiabetic potential of adzuki bean β-vignin via DPP IV inhibition. The lowest binding energy of the peptides was −6.03 kcal/mol. Digested adzuki bean β-vignin protein (10-1000 µg/mL) did not affect cell viability in the HepG2 cells, suggesting that the digest was not harmful to the cells. Treating the HepG2 cells with 1 mg/mL digested adzuki bean β-vignin protein significantly increased (p < 0.05) by over 40% and enhanced hepatic glucose uptake by more than 290% in healthy and insulin-resistant states. In addition, treating cells with 1 mg/mL digested adzuki bean β-vignin protein significantly increased (p > 0.05) the protein expression of human insulin receptor substrate 1 (IRS-1) by over 60%, AKT Serine/Threonine Kinase 1 (Akt-1) by over 70%, and glucose transporter 2 (Glut 2) by over 50% in both healthy and insulin-resistant states. Aim 2 evaluated the effects of adzuki bean-derived peptides, obtained after simulated gastrointestinal digestion, on markers of diabetes and elucidated the underlying mechanisms using an in vitro hepatic cell model, in comparison to those of soybean β-conglycinin peptides. Peptides Ile-Pro-Ala (IPA) and VP inhibited DPP IV (IPA Inhibitory Concentration (IC) 50, 7.86 μM; VP IC50, 9.58 μM). In-silico pharmacokinetic analysis revealed that PM (84.8 %) exhibited the highest absorption, and LLS exhibited the lowest absorption. All peptides did not exhibit AMES toxicity, suggesting that none of them were mutagenic. VP, PM, and IPA (1.78 nM-1.78 µM) did not affect the cell viability of HepG2 cells, with no significant difference from the untreated cells (p > 0.05), while peptide LLS (1.78 µM) significantly decreased the cell viability (89%, p < 0.05). Treating cells with 9.58 μM VP or 7.86 μM IPA significantly increased (p > 0.05) the protein expression of IRS-1, Akt-1, and Glut 2 in both healthy and insulin-resistant states, suggesting their potential in modulating insulin signaling and hepatic glucose uptake in both healthy and insulin-resistant states. In conclusion, the adzuki bean β-vignin digest, as well as the pure adzuki bean β-vignin and soybean β-conglycinin peptides effectively suppressed the DPP IV enzyme activities, stimulated the insulin signaling-Akt and glucose uptake pathways, resulting in improved T2D-related outcomes. This may contribute to the development of a adzuki bean-based ingredient with antidiabetic properties.

Graduation Semester

2025-08

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/130151

Copyright and License Information

© 2025 Shu Hang Kwan

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