TY - JOUR
T1 - Camel and bovine milk lactoferrins activate insulin receptor and its related AKT and ERK1/2 pathways
AU - Khan, Farheen Badrealam
AU - Anwar, Irfa
AU - Redwan, Elrashdy M.
AU - Palakkott, Abdulrasheed
AU - Ashraf, Arshida
AU - Kizhakkayil, Jaleel
AU - Iratni, Rabah
AU - Maqsood, Sajid
AU - Akli Ayoub, Mohammed
N1 - Funding Information:
We thank Ayesha Alneyadi for supplying us with fresh camel milk from a farm in Al Ain. We extend our sincere gratitude to Asma Al-Manhali, Amr Amin, and Khaled Masmoudi at the United Arab Emirates University (UAEU, Al Ain) for helping us with the cell culture facility and the ultracentrifuge. Author contributions: FK fractionated milk, performed bioluminescence resonance energy transfer (BRET), SDS-PAGE, and western blot experiments, analyzed the data, and wrote the manuscript; IA fractionated milk and contributed to cell transfection, BRET, and SDS-PAGE experiments; EMR purified and provided lactoferrin from camel milk; AP fractionated milk and contributed to cell transfection and SDS-PAGE experiments; AA contributed to cell transfection and SDS-PAGE experiments; JK contributed to SDS-PAGE and blot detection and quantification; RI contributed to SDS-PAGE, western blot experiments, and data analysis; SM contributed to milk fractionation and analysis of data with lactoferrin and in writing the discussion; MAA designed the project, performed BRET experiments, analyzed the data, and wrote and finalized the manuscript. This work was supported by a Center-based grant from Zayed Center for Health Sciences, UAEU (grant no. 31R235), and a UAEU postdoctoral grant (grant no. 31R241). The authors have not stated any conflicts of interest.
Publisher Copyright:
© 2022 American Dairy Science Association
PY - 2022/3
Y1 - 2022/3
N2 - Lactoferrin (LF) is a milk protein that may be an interesting candidate for the antidiabetic properties of milk due to its well-documented bioactivity and implication in diabetes. Here, we investigated the functional action of LF purified from camel and bovine milk (cLF, bLF) on insulin receptors (IR) and their pharmacology and signaling in hepatocarcinoma (HepG2) and human embryonic kidney (HEK293) cells. For this, we examined IR activation by bioluminescence resonance energy transfer (BRET) technology and the phosphorylation of its key downstream signaling kinases by western blot. The purified cLF and bLF induced phosphorylation of IR, AKT, and ERK1/2 in HepG2 and HEK293 cells. The BRET assays in HEK293 cells confirm the pharmacological action of cLF and bLF on IR, with a possible allosteric mode of action. This reveals for the first time the bioactivity of LF toward IR function, indicating it as a potential bioactive protein behind the antidiabetic properties of camel milk.
AB - Lactoferrin (LF) is a milk protein that may be an interesting candidate for the antidiabetic properties of milk due to its well-documented bioactivity and implication in diabetes. Here, we investigated the functional action of LF purified from camel and bovine milk (cLF, bLF) on insulin receptors (IR) and their pharmacology and signaling in hepatocarcinoma (HepG2) and human embryonic kidney (HEK293) cells. For this, we examined IR activation by bioluminescence resonance energy transfer (BRET) technology and the phosphorylation of its key downstream signaling kinases by western blot. The purified cLF and bLF induced phosphorylation of IR, AKT, and ERK1/2 in HepG2 and HEK293 cells. The BRET assays in HEK293 cells confirm the pharmacological action of cLF and bLF on IR, with a possible allosteric mode of action. This reveals for the first time the bioactivity of LF toward IR function, indicating it as a potential bioactive protein behind the antidiabetic properties of camel milk.
KW - bioluminescence resonance energy transfer (BRET)
KW - camel milk
KW - diabetes
KW - insulin receptor
KW - lactoferrin
UR - http://www.scopus.com/inward/record.url?scp=85121772642&partnerID=8YFLogxK
U2 - 10.3168/jds.2021-20934
DO - 10.3168/jds.2021-20934
M3 - Article
C2 - 34955280
AN - SCOPUS:85121772642
SN - 0022-0302
VL - 105
SP - 1848
EP - 1861
JO - Journal of Dairy Science
JF - Journal of Dairy Science
IS - 3
ER -
