Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance.
Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance.
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DOI：
10.1093/cei/uxad113
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发表时间：
2024-01-09
影响因子：
4.6
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中科院分区：
文献类型：
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甘露聚糖结合凝集素蛋白 (MBL) 水平升高表明，补体系统凝集素途径的激活有助于 1 型糖尿病 (T1D) 的血管病理学。伴有胰岛素抵抗 (IR) 的 T1D 个体的血管并发症最为严重，但 IR 是否会放大 T1D 中凝集素途径的激活尚不清楚。我们汇集了两项随机对照试验的治疗前数据，并对 46 名 T1D 个体进行了横断面分析。我们采用估计葡萄糖处理率 (eGDR)，这是一种经过验证的 IR 替代指标，其分界点为：<5.1、5.1–8.7 和 > 8.7 mg/kg/min 来确定 IR 状态，较低的 eGDR 值赋予较高程度的 IR。在 eGDR 分类之间比较 MBL 相关蛋白酶（MASP-1、MASP-2 和 MASP-3）及其调节蛋白 MAp44 的血浆水平。在 14 名个体的子集中，我们评估了 IR 改善后 MASP 和 MAp44 的变化。我们发现 MASP-1、MASP-2、MASP-3 和 MAp44 水平在 eGDR 阈值范围内呈阶梯式增加，MASP 和 MAp44 水平升高会导致更大程度的 IR。在 14 名患者的子集中，IR 的改善与 MASP 水平的显着降低相关，但与 MAp44 水平无关。总之，T1D 中的 IR 放大了 MASP-1/2/3 及其调节因子 MAp44 的水平，并且 IR 的改善使 MASP-1/2/3 水平正常化。鉴于这些蛋白质水平升高会导致血管病理学，补体系统凝集素途径的放大可能为了解 IR 与 T1D 血管并发症之间的关系提供机制见解。具有胰岛素抵抗的 1 型糖尿病患者血浆中甘露聚糖结合凝集素相关丝氨酸蛋白酶的水平升高。
Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pretreatment data from two RCTs and performed a cross-sectional analysis on 46 T1D individuals. We employed estimated glucose disposal rate (eGDR), a validated IR surrogate with cut-points of: <5.1, 5.1–8.7, and > 8.7 mg/kg/min to determine IR status, with lower eGDR values conferring higher degrees of IR. Plasma levels of MBL-associated proteases (MASP-1, MASP-2, and MASP-3) and their regulatory protein MAp44 were compared among eGDR classifications. In a subset of 14 individuals, we assessed change in MASPs and MAp44 following improvement in IR. We found that MASP-1, MASP-2, MASP-3, and MAp44 levels increased in a stepwise fashion across eGDR thresholds with elevated MASPs and MAp44 levels conferring greater degrees of IR. In a subset of 14 patients, improvement in IR was associated with significant reductions in MASPs, but not MAp44, levels. In conclusion, IR in T1D amplifies levels of MASP-1/2/3 and their regulator MAp44, and improvement of IR normalizes MASP-1/2/3 levels. Given that elevated levels of these proteins contribute to vascular pathology, amplification of the lectin pathway of the complement system may offer mechanistic insight into the relationship between IR and vascular complications in T1D. Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance.
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