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European Cytokine Network

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BTK targeting suppresses inflammatory genes and ameliorates insulin resistance Volume 31, issue 4, December 2020

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Authors
1 Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
2 Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
3 Ghassan Najeeb Pharaon hospital, Jeddah, Saudi Arabia
4 Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit, Egypt
* Correspondence: M. Althubiti, Mahmoud Zaki El-Readi

Type 2 diabetes (T2D) causes profound psychological and physical distress to patients and burdens the health-care system. Although several antidiabetic drugs have been approved, none of them are adequately effective in the long-term management of T2D. Therefore, novel treatment options are needed for disease prevention or delaying disease progression. Bruton's tyrosine kinase (BTK) is a cytoplasmic enzyme that plays a role in B-cell differentiation and proliferation, and therapeutic targeting of BTK offers protection against chronic diseases. In this study, we analyzed BTK expression and its correlation with inflammatory mediators in patients with diabetes and obesity. The levels of BTK were significantly high in visceral adipose tissues of patients (p < 0.01) with diabetes and obesity compared with healthy controls. Additionally, a positive correlation was noted between the expression of BTK and the inflammatory cytokine genes TNF-α, INF-γ, IL-6, and IL-1 (p < 0.01) in adipose tissue. In insulin-resistant HepG2 cells (IR-HepG2), ibrutinib inhibited BTK expression in parallel with inflammatory genes, and increased insulin signaling and activity compared with untreated IR-HepG2 cells. Additionally, ibrutinib-treated IR-HepG2 cells showed increased glucose uptake compared with untreated IR-HepG2 cells. These results provide evidence that BTK inhibition may serve as a novel therapeutic strategy for the treatment of T2D. These findings also uncover the novel role of BTK in diabetes and insulin resistance; however, further in vivo studies are required prior to translating the findings into clinical settings.

 
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