Hauwa'u Yakubu Bako1, Mohammed Auwal Ibrahim2, Muhammad Sani Isah3, Sani Ibrahim4. 1. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria; Department of Biochemistry, Kaduna State University, Kaduna, Nigeria. 2. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. Electronic address: mauwalibrahim@gmail.com. 3. Department of Medicine, Faculty of Clinical Sciences, College of Health Sciences, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. 4. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
Abstract
AIMS: Chronic inflammation is associated with the production of high levels of proinflammatory cytokines via the JAK-STAT and NF-κB signalling pathways which are known to be inhibited by tofacitinib and aspirin respectively. High levels of these cytokines increase the synthesis of suppressors of cytokines (SOCS), which at high levels inhibit insulin signalling leading to insulin resistance. The effects of tofacitinib and aspirin on the degree of insulin resistance in type 2 diabetic rats were determined. MATERIALS AND METHODS: Rats were induced with type 2 diabetes (T2D) by administration of 10% fructose solution (ad libitum) followed by streptozotocin injection (40 mg/kg BW) and treated with different doses of tofacitinib (10 and 20 mg/kg BW), aspirin (100 and 200 mg/kg BW) and combination of the two drugs at both doses for 9 weeks. KEY FINDINGS: Results showed that separate treatment with 10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin significantly (P < 0.05) decreased tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and serum amyloid A when compared to diabetic untreated rats. However, the combined therapy (10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin) significantly decreased the levels of TNF-α, IL-6, serum amyloid A, HOMA-IR, blood glucose level and SOC-3 gene expression but significantly (P < 0.05) improved glucose homoestasis, insulin secretion, HOMA-β and GLUT-4 gene expression when compared to diabetic untreated rat. CONCLUSION: It was concluded that simultaneous inhibition of the JAK-STAT and NF-κB signalling pathways with tofacitinib and aspirin respectively, could mitigate insulin resistance and hyperglycemia in T2D.
AIMS: Chronic inflammation is associated with the production of high levels of proinflammatory cytokines via the JAK-STAT and NF-κB signalling pathways which are known to be inhibited by tofacitinib and aspirin respectively. High levels of these cytokines increase the synthesis of suppressors of cytokines (SOCS), which at high levels inhibit insulin signalling leading to insulin resistance. The effects of tofacitinib and aspirin on the degree of insulin resistance in type 2 diabeticrats were determined. MATERIALS AND METHODS:Rats were induced with type 2 diabetes (T2D) by administration of 10% fructose solution (ad libitum) followed by streptozotocin injection (40 mg/kg BW) and treated with different doses of tofacitinib (10 and 20 mg/kg BW), aspirin (100 and 200 mg/kg BW) and combination of the two drugs at both doses for 9 weeks. KEY FINDINGS: Results showed that separate treatment with 10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin significantly (P < 0.05) decreased tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and serum amyloid A when compared to diabetic untreated rats. However, the combined therapy (10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin) significantly decreased the levels of TNF-α, IL-6, serum amyloid A, HOMA-IR, blood glucose level and SOC-3 gene expression but significantly (P < 0.05) improved glucose homoestasis, insulin secretion, HOMA-β and GLUT-4 gene expression when compared to diabetic untreated rat. CONCLUSION: It was concluded that simultaneous inhibition of the JAK-STAT and NF-κB signalling pathways with tofacitinib and aspirin respectively, could mitigate insulin resistance and hyperglycemia in T2D.
Authors: Jianhai Bi; Qiuchen Li; Zhigang Yang; Lei Cai; Tao Lv; Xun Yang; Li Yan; Xia Liu; Qian Wang; Xin Fu; Ran Xiao Journal: Front Cell Dev Biol Date: 2021-07-13