Abstract
The current study aims to investigate the antidiabetic efficacy of camel milk-derived lactoferrin and potential involvement of PPAR-γ and SIRT-1 via TLR-4/NFκB signaling pathway in obese diabetic pediatric population. Sixty young obese patients with type 2 diabetes were selected from the Pediatric Endocrine Metabolic Unit, Cairo University and were randomly divided among two age and sex-matched groups so as to receive either standard therapy without lactoferrin in one arm or to be treated with oral lactoferrin capsules (250 mg/day, p.o) for 3 months in the other arm. Both groups were compared to 50 control healthy volunteers. Measurements of HbA1c, lipid profile, antioxidant capacity (SOD, Nrf2), proinflammatory interleukins; (IL-1β, IL-6, IL-18), Cyclin D-1, lipocalin-2, and PPAR-γ expression levels were done at the beginning and 3 months after daily consumption of lactoferrin. The mechanistic involvement of TLR4-SIRT-1-NFκB signaling cascade was also investigated. The antidiabetic efficacy of lactoferrin was confirmed by significant improvement of the baseline levels of HbA1c, BMI and lipid profile of the obese pediatric cohort, which is evidenced by increased PPAR-γ and SIRT-1 expression. Moreover, the anti-inflammatory effect was evident by the significant decrease in serum levels of IL-1β, IL-6, IL-18, TNF-α, lipocalin 2 in type 2 diabetic post-treatment group, which corresponded by decreased NFκB downstream signaling indicators. The antioxidant efficacy was evident by stimulated SOD levels and NrF2 expression; compared with the pre-treatment group (all at P ≤ 0.001). The consumption of high concentrations of lactoferrin explains its hypoglycemic efficacy and counts for its insulin-sensitizing, anti-inflammatory and immunomodulatory effects via TLR4-NFκB-SIRT-1 signaling cascade. Recommendations on regular intake of lactoferrin could ensure better glycemic control, compared to conventional antidiabetics alone.
Highlights
Despite established therapies for type 2 diabetes mellitus (T2DM), the occurrence of insulin resistance and glucose level fluctuations remains a challenge [1]
IL-18 is one of the mediators of innate immunity initiated by host–pathogen interaction, which is mainly produced by monocytes/ macrophages in response to stimuli of viral/bacterial origin [11]
The tested lactoferrin was intended to be derived from camel milk colostrums, requested a special formula of Jarrow Formulas® derived from the colostrums of camel milk
Summary
Despite established therapies for type 2 diabetes mellitus (T2DM), the occurrence of insulin resistance and glucose level fluctuations remains a challenge [1]. Type 2 diabetes is thought to involve chronic. IL-6 is a pleiotropic cytokine with a major role as immunoregulator and non-immune cell types and tissues as fibroblasts, endothelial cells, monocytes/macrophages, and a variety of tumor cell lines [10]. IL-18 is one of the mediators of innate immunity initiated by host–pathogen interaction, which is mainly produced by monocytes/ macrophages in response to stimuli of viral/bacterial origin [11]. Concerning the reported hypoglycemic effect of camel milk, it is attributed to the high amount of insulin as well as the presence of bioactive compounds in milk [12,13,14,15,16], like lactoferrin, which is deemed responsible for most of its therapeutic effects
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