Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on Isolated Human Pancreatic Islets.
Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on Isolated Human Pancreatic Islets.
复制标题
DOI：
10.1021/acs.jproteome.7b00160
复制
发表时间：
2017-06-02
影响因子：
4.4
通讯作者：
Buchwald P
中科院分区：
文献类型：
--
作者：
Garcia-Contreras M;Tamayo-Garcia A;Pappan KL;Michelotti GA;Stabler CL;Ricordi C;Buchwald P
人胰岛移植是一种治疗1型糖尿病患者谁经历严重低血糖的可能性。然而，移植前后胰岛活力和功能的丧失是限制疗效的主要障碍。为了研究炎症和缺氧的影响，这是阻碍分离、培养和移植胰岛存活和功能的主要障碍，我们对人类胰岛进行了全面的代谢组学评估，同时进行了动态葡萄糖刺激胰岛素释放（GSIR）灌注研究，以进行功能评估。培养基和细胞样本的代谢组学分析分别鉴定出总共241种和361种生化物质。代谢产物以高度显著的方式改变，例如，炎症下的犬尿氨酸、犬尿氨酸、瓜氨酸和甘露醇/山梨醇（均升高）以及缺氧时的乳酸（升高）和n -甲酰蛋氨酸（降低）。动态GSIR实验捕获了第一阶段和第二阶段胰岛素释放，发现缺氧条件下胰岛素分泌严重下降，而暴露于炎症细胞因子混合物（IL-1β， IFN-γ和TNF-α）的胰岛的基线水平升高和胰岛素分泌受到刺激。由于在犬尿氨酸和犬尿酸中观察到独特的大变化，它们可能作为胰岛炎症的潜在生物标志物，而相应途径上的IDO可能是一个有价值的治疗靶点，以抑制炎症效应。
The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation. Metabolomics profiling of media and cell samples identified a total of 241 and 361 biochemicals, respectively. Metabolites that were altered in highly significant manner in both included, for example, kynurenine, kynurenate, citrulline, and mannitol/sorbitol under inflammation (all elevated) plus lactate (elevated) and N-formylmethionine (depressed) for hypoxia. Dynamic GSIR experiments, which capture both first- and second-phase insulin release, found severely depressed insulin-secretion under hypoxia, whereas elevated baseline and stimulated insulin-secretion was measured for islet exposed to the inflammatory cytokine cocktail (IL-1β, IFN-γ, and TNF-α). Because of the uniquely large changes observed in kynurenine and kynurenate, they might serve as potential biomarkers of islet inflammation, and IDO on the corresponding pathway could be a worthwhile therapeutic target to dampen inflammatory effects.
登录
查看更多内容
胰腺β细胞对促炎细胞因子的反应性死亡不同于真正的细胞凋亡。
影响因子：
3.7
作者：
Collier JJ;Burke SJ;Eisenhauer ME;Lu D;Sapp RC;Frydman CJ;Campagna SR
通讯作者：
Campagna SR
影响因子：
--
作者：
Buchwald P
通讯作者：
Buchwald P
影响因子：
3.3
作者：
Cabrera, Over;Jacques-Silva, M. Caroline;Caicedo, Alejandro
通讯作者：
Caicedo, Alejandro
影响因子：
7.7
作者：
DIONNE, KE;COLTON, CK;YARMUSH, ML
通讯作者：
YARMUSH, ML
影响因子：
11.4
作者：
Görlach A;Dimova EY;Petry A;Martínez-Ruiz A;Hernansanz-Agustín P;Rolo AP;Palmeira CM;Kietzmann T
通讯作者：
Kietzmann T