摘要:
脂肪细胞的功能紊乱与糖尿病的发生有关。近来有研究表明，脂肪组织不仅仅是储存脂肪和调节脂类代谢的组织，同时也是最大的免疫功器官，脂肪细胞可通过分泌细胞因子来影响免疫功能。特异性敲除了脂肪细胞的SUMO特异蛋白酶SENP1基因的小鼠会出现I型糖尿病(type-1 diabetes mellitus, T1DM)的症状。胰腺周围脂肪组织(peri-pancreatic adipocytes, PATs)在胰腺功能中发挥了全身效应以及旁分泌作用与糖尿病的发生密切相关。胰腺周围的脂肪组织与其他脂肪储存组织相比，产生了更多的促炎细胞因子。这些促炎细胞因子对胰岛有直接的细胞毒性作用，导致邻近胰岛的炎症反应，破坏胰腺中的免疫平衡。NF-κB必要分子(NF-κB essential molecule, NEMO) SUMO化，可以增强NF-κB活性、细胞因子产生以及胰腺的炎症反应。NF-κB抑制剂为阻断炎症反应、缓解1型糖尿病提供了新的治疗策略。因此胰腺周围脂肪组织的脂肪细胞在糖尿病发生时的胰腺免疫调节建立中可能起着重要作用，为I型糖尿病的发生发展提供了可能的新的分子发病机制。
Abstract:
Adipocyte dysfunction correlates with the development of diabetes. Recent studies suggest that adipose tissue is not simply the organ that stores fat and regulates lipid metabolism, but also is the largest endocrine organ with immune functions. Mice with an adipocyte-specific deletion of a SUMO- specific protease SENP1 develop symptoms of type-1 diabetes mellitus (T1DM) resulted from beta cell damage. Cytokine profiling indicates that peri-pancreatic adipocytes (PATs) of SENP1-dificient mice have increased proinflammatory cytokine production compared with other adipose depots. Proinflammatory cytokines originated from PATs have direct cytotoxic effects on pancreatic islets, and also increase infiltration of immune cells by augmenting CCL5 expression in adjacent pancreatic islets. Molecular analyses support that SUMOylation of NF-κB essential molecule (NEMO) in PATs leads to increased NF-κB activity, cytokine production and pancreatic inflammation. Therapeutic attempting to ameliorate the T1DM phenotype should consider using of NF-κB inhibitor against adipocyte inflammation.