Influence of anti-fibrillation TNGQ peptide and rutin combination on β-cell cytoprotective effects against IAPP-induced cell death and oxidative stress.

Biochem Biophys Res Commun

School of Nutrition Sciences, Health Sciences, University of Ottawa, Ottawa, K1H 8M5, Canada; Department of Chemistry and Biomolecular Sciences, Science, University of Ottawa, Ottawa, Ontario, K1N 6N5, Canada; University Food Properties and Nutrient Bioavailability, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada. Electronic address:

Published: December 2024

AI Article Synopsis

  • Type 2 diabetes is linked to IAPP fibrillation, which damages pancreatic β-cells through oxidative stress and membrane disruption.
  • Rutin, a plant polyphenol, and certain bioactive peptides (TNGQ, MANT, YMSV) show promise as inhibitors for IAPP fibrillation.
  • The study found that combining rutin with TNGQ significantly reduced IAPP fibrillation and related cell toxicity, suggesting potential for creating new anti-diabetic nutraceuticals.

Article Abstract

Type 2 diabetes development has been associated with islet amyloid polypeptide (IAPP) fibrillation. IAPP fibrils have various deleterious effects, such as oxidative stress and disruption of cellular membrane integrity, resulting in pancreatic β-cell toxicity. Rutin, a plant polyphenol, possesses promising cytoprotective effects as a fibrillation inhibitor. Similarly, bioactive peptides have been identified as potential inhibitors to IAPP fibrillation. In this study, the effect of peptide/polyphenol mixtures consisting of rutin and each peptide, TNGQ, MANT, and YMSV, on anti-fibrillation activity and cellular response was elucidated. Results indicated a 54.7-75.1 % decrease in thioflavin T fluorescence, confirming anti-fibrillation activity. The combination decreased the average particle diameters of IAPP more than the single inhibitors, suggesting a combined effect of peptide/rutin mixtures in enhancing anti-fibrillation activity. IAPP fibrillation-induced rat insulinoma RIN-m cell death was minimized in the presence of the peptide/rutin mixture, but the activity was lower relative to rutin alone, suggesting a non-additive effect of the mixtures. Transmission electron microscopy showed a near-complete inhibition of IAPP fibrillation by TNGQ/rutin mixtures, which translated to a decreased production of membrane-bound IAPP oligomers in RIN-m cells based on immunofluorescence staining. Additionally, TNGQ/rutin mixtures significantly decreased reactive oxygen species production by 30 %, higher than the effects of single inhibitors, but no effect was observed on glucose-stimulated insulin secretion. The results demonstrate the potential of multifunctional compounds as dual inhibitor systems in controlling IAPP fibrillation and provide insight into the implications of peptide/polyphenol mixtures towards the rational development of novel anti-diabetic nutraceutical combinations.

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Source
http://dx.doi.org/10.1016/j.bbrc.2024.150976DOI Listing

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