Abstract

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.

Highlights

  • Camel milk (CM) is traditionally thought to have many nutritional and medicinal virtues, including antidiabetic effects, in certain tribes and countries

  • LF Purified from CM and bovine milk (BM) Promoted insulin receptors (IR) Activation in HEK293 Cells as Assessed by bioluminescence resonance energy transfer (BRET)

  • Synergistic Effects of LF Purified from CM and BM on Insulin-Mediated IR Activation in HEK293 Cells as Assessed by BRET

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Summary

Introduction

Camel milk (CM) is traditionally thought to have many nutritional and medicinal virtues, including antidiabetic effects, in certain tribes and countries. Khan et al.: CAMEL AND BOVINE MILK LACTOFERRINS AND INSULIN proteins and peptides in CM whey fractions, targeting the key pathways of glucose homeostasis and regulation that may provide a molecular basis for the antidiabetic effects of CM (Ayoub et al, 2018). All these in vitro data have yet to be proven in vivo and in more integrated systems, and further studies are required to demonstrate whether the CM products of degradation resulting from digestion have similar mechanisms. Such a case needs to be tested experimentally, and any clinical application of LF should consider intraperitoneal or intravenous injection of the bioactive LF-derived peptides

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