Functional significance of food-derived peptides in inhibiting islet amyloid polypeptide (IAPP) fibrillation in Type 2 diabetes management

Tuesday, April 30, 2024

10:55 AM – 11:15 AM EDT

Room: 520b

Presenting Author(s)

Raliat O. Abioye, BSc (Hons) (she/her/hers)

PhD Candidate
University of Ottawa
Nepean, ON, Canada

Co-Author(s)

MY

Martha Yiridoe

Undergraduate Student
University of Ottawa, United States
MD

Mόnica Delgado Martínez

Undergraduate Student
University of Ottawa, Canada
Ogadimma D. Okagu, PhD candidate

Researcher
University of Ottawa
Ottawa, Ontario, Canada
Rotimi E. Aluko, PhD (he/him/his)

Professor
University of Manitoba
Winnipeg, MB, Canada
Chibuike Udenigwe, PhD

Full Professor & University Research Chair
University of Ottawa, Ontario, Canada

Abstract: Islet amyloid polypeptide (IAPP) fibrillation has been commonly associated with the exacerbation of type 2 diabetes. Consequently, inhibition of IAPP fibrillation to minimize β-cell cytotoxicity is an important approach towards β-cell preservation and type 2 diabetes management. Three tetrapeptides, TNGQ, MANT, and YMSV, were initially studied for their effect on IAPP fibrillation and cellular membrane integrity. Using thioflavin T (ThT) fluorescence assay, circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), molecular docking, and membrane leakage assays, we evaluated the potential anti-fibrillation mechanism and cytoprotective effects of the tetrapeptides. ThT fluorescence kinetics and microscopy and transmission electron microscopy showed that all three tetrapeptides showed varying anti-fibrillation activity with TNGQ being the most effective inhibitor. Molecular docking showed that TNGQ and MANT interact with monomeric IAPP via hydrogen bonding and electrostatic interaction. Giant unilamellar vesicles were used to demonstrate the cytoprotective effects of the tetrapeptides in the presence of IAPP. Following the trend, TNGQ produced the lowest fluorescence intensity and percent leakage and was the best at maintaining membrane integrity over 12 h, suggesting the role of peptide structure on anti-fibrillation activity. Molecular docking of the tetrapeptides to oligomeric IAPP fibrillar intermediate highlights the importance of binding to the C-terminal region for fibrillation inhibition. The findings provide insight into the preferred structural features of anti-IAPP fibrillation peptide inhibitors, towards the rational development of novel anti-diabetic peptides with anti-fibrillation mechanisms.