更多证据表明2型糖尿病是一种炎性疾病

发表在Journal of Leukocyte Biology的一项最新研究表明，巨噬细胞能够侵入糖尿病患者的胰腺，产生大量有助于消除胰岛素产生细胞（β细胞）的细胞因子。这些研究成果进一步支持了“2型糖尿病是一种炎性疾病”的观念。

　　

生物通报道：随着人们的腰围增加，2型糖尿病的发病率也在增加。现在，对于到底人体内发生了什么从而导致了2型糖尿病，并可能导致一些疾病相关的并发症，科学家们已经有了一个更好的了解，如Nature子刊：SLC30A8基因功能缺失性突变可预防2型糖尿病。最近，丹麦的科学家们在小鼠中发现，在疾病的早期阶段，巨噬细胞——一种特殊类型的免疫细胞，会侵入糖尿病患鼠的胰腺组织。然后，这些炎症细胞产生了大量的促炎性蛋白，称为细胞因子，它们直接有助于胰腺内胰岛素产生细胞（β细胞）的消除，从而导致糖尿病。这项研究成果发表在2014年1月份的Journal of Leukocyte Biology杂志。

丹麦诺和诺德公司糖尿病并发症生物学部门的Alexander Rosendahl博士参与了这项研究工作，他说：“这项研究可以为研究人员提供新的见解，使我们研发出特制的抗炎为基础的治疗方法，降低2型糖尿病患者的负担。这些新的疗法，被证实能够补充现有的治疗方法，如胰岛素和GLP-1类似物。”

为了得到这些研究结果，科学家们将自发发展为糖尿病的肥胖小鼠，与健康小鼠进行了比较分析。从很小的年龄开始，那时肥胖小鼠仅仅表现早期的糖尿病，到它们在多个器官中表现全身性并发症的年龄，对其进行跟踪调查。研究人员利用最先进的流式细胞技术（允许在单细胞水平上进行评估），评估了巨噬细胞在胰腺和脾脏中β细胞周围的存在。在早期和晚期阶段，糖尿病小鼠都比健康小鼠表现出显著的变化。

Journal of Leukocyte Biology的副主编John Wherry博士说：“了解肥胖和2型糖尿病的研究人员越多，就似乎越能表明，炎症在这类疾病的进展和严重程度中起着至关重要的作用。这项研究阐明，一种关键的炎性细胞是如何与疾病产生关联的，也清楚地显示出，当有人患2型糖尿病时，有哪些地方可能出了毛病。从这些研究中所获得的知识，为开发减轻这种疾病严重程度的免疫新疗法，带来了希望。”（生物通：王英）

生物通推荐原文摘要：
Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization
Abstract: Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80−) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80− islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80− macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86low macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.