Abstract
Type 2 diabetes mellitus (T2DM) is a multifactorial disease that requires multiple therapeutic strategies for its management. Bioactive peptides with multiple anti-diabetic targets are attractive therapeutic molecules. The present study was conducted to identify additional anti-diabetic targets of α-glucosidase inhibitory peptides, SVPA, SEPA, STYV, and STY. The α-glucosidase inhibitory activity of the peptides was in the order STYV > STY > SEPA > SVPA while molecular docking against human dipeptidyl peptidase IV (DPP-IV) showed that SVPA had the best binding affinity. In contrast, in vitro studies indicated that SEPA had a significantly higher (P < 0.05) DPP-IV inhibitory activity (IC50 = 5.78 ± 0.19 mM) than other peptides. SVPA and SEPA showed mixed inhibition pattern while STYV and STY were uncompetitive inhibitors of the enzyme. IPI (diprotin A), STYV and STY were not cytotoxic while SEPA displayed some cytotoxicity. In differentiated 3T3-L1 adipocytes, SVPA and STYV were found to induce a significant (P < 0.05) decrease in intracytoplasmic lipid accumulation when added during the differentiation process while STY, GSH and IPI caused significant reduction (P < 0.05) in the lipid accumulation when added after the differentiation. The SVPA, SEPA and STYV were better scavengers of methylglyoxal than STY but STYV had the best scavenging activities toward reactive oxygen species and nitric oxide. It was concluded that the four α-glucosidase inhibitory peptides including IPI have multiple targets against type T2DM but, overall, of the four peptides evaluated, STYV tends to have better potential for application as a multifunctional anti-diabetic peptide.
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Acknowledgements
We acknowledge the National Research Foundation of South Africa and the University of Pretoria for financial support. The first author also acknowledges the University of Pretoria for the award of a postdoctoral fellowship position in Biochemistry and Ahmadu Bello University, Zaria, Nigeria for the award of a study fellowship.
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The study was funded by the National Research Foundation of South Africa (Grant Number 91052).
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Mohammed Auwal Ibrahim, June Serem, Megan Bester, Albert Neitz and Anabella Gaspar have declared that they have no conflict of interest.
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Ibrahim, M.A., Serem, J.C., Bester, M.J. et al. New Antidiabetic Targets of α-Glucosidase Inhibitory Peptides, SVPA, SEPA, STYV and STY: Inhibitory Effects on Dipeptidyl Peptidase-IV and Lipid Accumulation in 3T3-L1 Differentiated Adipocytes with Scavenging Activities Against Methylglyoxal and Reactive Oxygen Species. Int J Pept Res Ther 26, 1949–1963 (2020). https://doi.org/10.1007/s10989-019-09993-2
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DOI: https://doi.org/10.1007/s10989-019-09993-2