Infliximab is a chimeric monoclonal IgG1 antibody that specifically binds to TNF-α. Infliximab prevents the interaction of TNF-α with TNF-α receptor (TNFR1 and TNFR2). Infliximab has the potential for autoimmune, chronic inflammatory diseases and diabetic neuropathy research[1][2]. So, infliximab is a medication used to treat patients with autoimmune and chronic inflammatory diseases[5].
infliximab has been also shown to improve insulin resistance[3]. In vitro,infliximab ameliorates TNF-alpha-induced insulin resistance in 3T3L1 adipocytes in vitro by restoring phosphorylation of key mediators of the insulin signaling pathway such as IRS-2 and AKT via PTP1B inhibition that in consequence improves insulin-dependent glucose uptake in these adipose cells[4]
Diabetic mice showed significant impairments in SNCV and MNCV at 8 weeks. Diabetic mice treated with saline showed no improvement in SNCV or MNCV at 12 weeks, whereas diabetic mice treated with infliximab showed significant improvement at this time (4 weeks after infliximab treatment). In conclusion a single injection of infliximab leads to marked improvement in diabetic neuropathy[7].Infliximab reduces the levels of serum insulin, fasting glucose and insulin resistance in patients with ankylosing spondylitis and rheumatoid arthritis[6]
参考文献:
[1]. Lis K, Kuzawińska O, et,al. Tumor necrosis factor inhibitors - state of knowledge. Arch Med Sci. 2014 Dec 22;10(6):1175-85. doi: 10.5114/aoms.2014.47827. PMID: 25624856; PMCID: PMC4296073.
[2]. Yamakawa I, Kojima H, Terashima T, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998.
[3]. Burska AN, Sakthiswary R, et,al. Effects of Tumour Necrosis Factor Antagonists on Insulin Sensitivity/Resistance in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. PLoS One. 2015 Jun 25;10(6):e0128889. doi: 10.1371/journal.pone.0128889. PMID: 26110878; PMCID: PMC4482317.
[4]. Méndez-García LA, Trejo-Millán F, et,al.Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by attenuating PTP1B activation in 3T3L1 adipocytes in vitro. Scand J Immunol. 2018 Nov;88(5):e12716. doi: 10.1111/sji.12716. Epub 2018 Oct 10. PMID: 30260514.
[5]. Antoni C, Krueger GG, et,al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005 Aug;64(8):1150-7. doi: 10.1136/ard.2004.032268. Epub 2005 Jan 27. PMID: 15677701; PMCID: PMC1755609.
[6]. Stagakis I, Bertsias G, et,al.Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther. 2012 Jun 12;14(3):R141. doi: 10.1186/ar3874. PMID: 22691241; PMCID: PMC3446524.
[7]. Yamakawa I, Kojima H, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998.
英夫利昔单抗是一种嵌合单克隆 IgG1 抗体，可特异性结合 TNF-α。英夫利昔单抗阻止 TNF-α 与 TNF-α 受体（TNFR1 和 TNFR2）的相互作用。英夫利昔单抗具有用于自身免疫、慢性炎症性疾病和糖尿病神经病变研究的潜力[1][2]。因此，英夫利昔单抗是一种用于治疗自身免疫性疾病和慢性炎症性疾病的药物[5]。
英夫利昔单抗也被证明可以改善胰岛素抵抗[3]。在体外，英夫利昔单抗通过 PTP1B 抑制恢复胰岛素信号通路关键介质（如 IRS-2 和 AKT）的磷酸化，从而改善这些脂肪细胞中胰岛素依赖性葡萄糖摄取，从而改善 3T3L1 脂肪细胞中 TNF-α 诱导的胰岛素抵抗细胞[4]
糖尿病小鼠在 8 周时显示 SNCV 和 MNCV 显着受损。用盐水治疗的糖尿病小鼠在 12 周时未显示 SNCV 或 MNCV 改善，而用英夫利昔单抗治疗的糖尿病小鼠此时显示出显着改善（英夫利昔单抗治疗后 4 周）。总之，单次注射英夫利昔单抗可显着改善糖尿病神经病变[7]。英夫利昔单抗可降低强直性脊柱炎和类风湿性关节炎患者的血清胰岛素、空腹血糖和胰岛素抵抗水平[ 6]
| Cell experiment [1]: | |
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Cell lines |
3T3L1 mature adipocytes |
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Preparation Method |
Adipocytes were stimulated twice at zero and 60 minutes with 2 μmol L 1 insulin. Adipocytes were stimulated with 10 ng/mL infliximab at the beginning of the 2-hour in vitro assay. 3T3L1 adipocytes were collected every 20 minutes for 2 hour. |
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Reaction Conditions |
10 ng/mL infliximab at the beginning of the 2-hour in vitro assay |
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Applications |
Infliximab restores insulin-dependent glucose uptake, phosphorylation of the insulin signaling pathway and attenuates TNF-alpha-induced PTP1B activation in TNF-α-treated 3T3L1 adipocytes. |
| Animal experiment [2]: | |
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Animal models |
Eight-week-old C57BL/6J (WT, TNF-α+/+) and TNF-α-deficient (TNFα?/?) mice of strain B6 |
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Preparation Method |
Infliximab was injected into diabetic and normal mice for 4 weeks |
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Dosage form |
Infliximab 10 μg/g in 100 μl saline for 4 weeks |
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Applications |
Diabetic mice showed significant impairments in SNCV and MNCV at 8 weeks. Diabetic mice treated with saline showed no improvement in SNCV or MNCV at 12 weeks, whereas diabetic mice treated with infliximab showed significant improvement at this time (4 weeks after infliximab treatment). |
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参考文献: [1]. Méndez-García LA, Trejo-Millán F, Martínez-Reyes CP, Manjarrez-Reyna AN, Esquivel-Velázquez M, Melendez-Mier G, Islas-Andrade S, Rojas-Bernabé A, Kzhyshkowska J, Escobedo G. Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by attenuating PTP1B activation in 3T3L1 adipocytes in vitro. Scand J Immunol. 2018 Nov;88(5):e12716. doi: 10.1111/sji.12716. Epub 2018 Oct 10. PMID: 30260514. [2]. Yamakawa I, Kojima H, et,al.Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E844-52. doi: 10.1152/ajpendo.00029.2011. Epub 2011 Aug 2. PMID: 21810933; PMCID: PMC3213998./p> |
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