TY - JOUR
T1 - 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
AU - Ashraf, Arshida
AU - Mudgil, Priti
AU - Palakkott, Abdulrasheed
AU - Iratni, Rabah
AU - Gan, Chee Yuen
AU - Maqsood, Sajid
AU - Ayoub, Mohammed Akli
N1 - Funding Information:
This work was supported by a United Arab Emirates University (UAEU) startup grant (31S305) and a UAEU-Zayed Center for Health Sciences (ZCHS) grant (31R235) to MAA, UAEU Program for Advanced Research (UPAR) grant (31F094) to SM, and Universiti Sains Malaysia Research University Individual (USM RUI) grant (1001/CABR/8011045) to CG. Hassan M. Hassan (Department of Food, Nutrition and Health, College of Food and Agriculture, UAEU) is acknowledged for performing reverse-phase ultra performance liquid chromatography analysis of the hydrolysates. AA performed BRET, phosphorylation, and glucose uptake experiments; PM fractionated camel milk and characterized the hydrolysates and performed the DPP-IV assay; AP contributed to cell transfection, phosphorylation, and glucose uptake experiments; RI contributed to cell transfection, phosphorylation experiments, and data analysis; CG performed peptide sequencing; SM designed the project, performed in silico analysis, analyzed the data, and wrote and finalized the manuscript; and MAA designed the project, performed BRET experiments, analyzed the data, and wrote and finalized the manuscript. There are no conflicts of interest to declare.
Publisher Copyright:
© 2021 American Dairy Science Association
PY - 2021/1
Y1 - 2021/1
N2 - The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.
AB - The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.
KW - DPP-IV
KW - camel milk
KW - diabetes
KW - insulin receptor
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U2 - 10.3168/jds.2020-18627
DO - 10.3168/jds.2020-18627
M3 - Article
C2 - 33162074
AN - SCOPUS:85095572916
SN - 0022-0302
VL - 104
SP - 61
EP - 77
JO - Journal of Dairy Science
JF - Journal of Dairy Science
IS - 1
ER -