Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Front Endocrinol (Lausanne). 2021 Jul 29;12:652942. doi: 10.3389/fendo.2021.652942. eCollection 2021.
Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-13, and IL-10. The study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37°C and 5% CO: 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants ( = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-α () and IFN-γ (p < 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM.
2 型糖尿病（T2DM）与慢性低度炎症有关，其特征是先天和适应性免疫反应失调。因此，通过免疫调节剂降低炎症水平可能在 T2DM 治疗中发挥作用。丁酸盐是最有效的短链脂肪酸（SCFA），它通过抑制组蛋白去乙酰化酶活性发挥抗炎作用。作为一种免疫调节剂，丁酸钠可以抑制核因子 kB（NF-kB）的激活，并减少免疫细胞中促炎细胞因子的产生。本研究旨在测量控制不佳的 T2DM 和血糖正常的参与者的血浆丁酸盐水平，并通过测量以下细胞因子的产生来比较两组外周血单核细胞（PBMC）对丁酸钠治疗的反应：肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、干扰素（IFN）-γ、IL-13 和 IL-10。该研究检查了 15 名控制不佳的 T2DM 参与者和 15 名血糖正常的参与者的 PBMC。将 PBMC 在 37°C 和 5%CO 的温度下培养两天，用以下刺激物进行培养：100ng/ml 脂多糖（LPS）、1mM 丁酸钠或 100ng/ml LPS 和 1mM 丁酸钠的组合。使用气相色谱-质谱法测量血浆丁酸盐，使用磁珠多重分析测定培养上清液中的细胞因子。控制不佳的 T2DM 参与者的血浆丁酸盐水平与血糖正常的参与者无显著差异（=0.105）。与 LPS 刺激的 PBMC 培养物相比，用 1mM 丁酸钠处理可降低血糖正常参与者 TNF-α（）和 IFN-γ（p<0.038）的水平。在控制不佳的 T2DM 患者的 PBMC 中也出现了相同的总体趋势，但较高的变异性似乎排除了统计学意义。这些数据表明，丁酸盐可能调节人 PBMC 中炎症细胞因子的产生，但需要进一步研究以确定丁酸盐在控制不佳的 T2DM 中是否具有抗炎作用。
