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 afnity. In contrast, in vitro
studies indicated that SEPA had a signifcantly higher (P<0.05) DPP-IV inhibitory activity (IC50=5.78±0.19 mM) than
other pe... More
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 afnity. In contrast, in vitro
studies indicated that SEPA had a signifcantly 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 diferentiated
3T3-L1 adipocytes, SVPA and STYV were found to induce a signifcant (P<0.05) decrease in intracytoplasmic lipid accumulation
when added during the diferentiation process while STY, GSH and IPI caused signifcant reduction (P<0.05) in
the lipid accumulation when added after the diferentiation. 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
