Molecular basis of the anti-diabetic properties of camel milk through profiling of its bioactive peptides on dipeptidyl peptidase Ⅳ (DPP-Ⅳ) and insulin receptor activity

摘要

The molecular basis of the anti-diabetic propertiesof camel milk reported in many studies and the exactactive agent are still elusive. Recent studies have reportedeffects of camel whey proteins (CWP) and theirhydrolysates (CWPH) on the activities of dipeptidylpeptidase Ⅳ (DPP-Ⅳ) and the human insulin receptor(hIR). In this study, CWPH were generated, screenedfor DPP-Ⅳ binding in silico and inhibitory activity invitro, and processed for peptide identification. Furthermore,pharmacological action of intact CWP and theirselected hydrolysates on hIR activity and signaling andon glucose uptake were investigated in cell lines. Resultsshowed inhibition of DPP-IV by CWP and CWPH andtheir positive action on hIR activation and glucose uptake.Interestingly, the combination of CWP or CWPHwith insulin revealed a positive allosteric modulationof hIR that was drastically reduced by the competitivehIR antagonist. Our data reveal for the first timethe profiling and pharmacological actions of CWP andtheir derived peptides fractions on hIR and their pathwaysinvolved in glucose homeostasis. This sheds morelight on the anti-diabetic properties of camel milk byproviding the molecular basis for the potential use ofcamel milk in the management of diabetes.