Magnetic ligand fishing using immobilized DPP-IV for identification of antidiabetic ligands in lingonberry extract.

In this work, a new magnetic ligand fishing probe for discovery of DPP-IV inhibitory ligands was developed and it was tested as a proof of concept on the fruit extract of Vaccinium vitis-idaea (lingonberry). The ligands were shown to have appreciable dipeptidyl peptidase IV (DPP-IV) inhibitory activity (IC50: 31.8 µg mL-1).) Inhibition of DPP-IV is a well-known therapeutic approach for management of type 2 diabetes (T2D). DPP-IV was successfully immobilized onto magnetic beads and was shown to retain its catalytic activity and selectivity over a model mixture. A total of four ligands were successfully fished out and identified as cyanidin-3-galactoside (2), cyanidin-3-arabinoside (3), proanthocynidin A (4), and 10-carboxyl-pyranopeonidin 3-O-(6″-O-p-coumaroyl)-glucoside (5) using HPLC/HRMS.

Peptides from chicken processing by-product inhibit DPP-IV and promote cellular glucose uptake: potential ingredients for T2D management.

Inhibition of dipeptidyl peptidase IV (DPP-IV) and stimulation of muscle glucose uptake are two of the key strategies for management of type-2-diabetes (T2D). In the present study, four protein hydrolysates generated by enzymatic hydrolysis of chicken by-product, i.e., mechanical chicken deboning residue, were evaluated for their DPP-IV inhibitory activity as well as their effect on glucose uptake by skeletal muscle cells. The DPP-IV inhibitory assay was performed at two concentrations (1000 µg mL-1 and 10 µg mL-1) for the crude chicken protein hydrolysates. The hydrolysate with the highest DPP-IV inhibition was selected for preparative-scale fractionation using size-exclusion chromatography (SEC). The SEC fractions were tested for DPP-IV inhibitory activity as well as their effect on glucose uptake and metabolic activity of skeletal muscle cells. The muscle cells were treated with the SEC fractions and glucose uptake was measured based on luminescence detection of 2-deoxyglucose-6-phosphate (2DG6P). A fraction with peptides in the lower molecular weight range was shown to promote glucose uptake and to inhibit DPP-IV. Further chromatographic fractionation followed by inhibition assaying of the most potent SEC fraction led to isolation of five refined peptide fractions with more than 80% DPP-IV inhibition, which were subsequently analyzed with LC-HRMS/MS. This led to identification of 14 peptides as potential DPP-IV inhibitors from protein hydrolysates of mechanical chicken deboning residue.