The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes.
The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes.
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DOI：
10.1016/j.molmet.2017.06.004
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发表时间：
2017-08
影响因子：
8.1
通讯作者：
Wolf E
中科院分区：
文献类型：
--
作者：
Blutke A;Renner S;Flenkenthaler F;Backman M;Haesner S;Kemter E;Ländström E;Braun-Reichhart C;Albl B;Streckel E;Rathkolb B;Prehn C;Palladini A;Grzybek M;Krebs S;Bauersachs S;Bähr A;Brühschwein A;Deeg CA;De Monte E;Dmochewitz M;Eberle C;Emrich D;Fux R;Groth F;Gumbert S;Heitmann A;Hinrichs A;Keßler B;Kurome M;Leipig-Rudolph M;Matiasek K;Öztürk H;Otzdorff C;Reichenbach M;Reichenbach HD;Rieger A;Rieseberg B;Rosati M;Saucedo MN;Schleicher A;Schneider MR;Simmet K;Steinmetz J;Übel N;Zehetmaier P;Jung A;Adamski J;Coskun Ü;Hrabě de Angelis M;Simmet C;Ritzmann M;Meyer-Lindenberg A;Blum H;Arnold GJ;Fröhlich T;Wanke R;Wolf E
糖尿病和相关并发症的发病率正在稳步上升。作为研究慢性胰岛素不足和高血糖症的全身性后果的资源，我们建立了长期糖尿病INSC 94 Y转基因猪、突变INS基因诱导的青年糖尿病（MIDY）模型和野生型（WT）同窝仔的综合生物库。将雌性MIDY猪（n = 4）与雌性WT同窝仔（n = 5）一起用次优胰岛素治疗维持2年。血浆胰岛素，C-肽和胰高血糖素水平定期测定使用特定的免疫测定。此外，还进行了临床化学、靶向代谢组学和脂质组学分析。在2岁时，对所有猪实施安乐死、尸检，并通过系统统一随机取样程序采集广谱组织。通过体视学方法测定总β细胞体积。通过无标记蛋白质组学对胰腺、肝脏和肾皮质进行了初步蛋白质组学分析。MIDY猪的空腹血糖和果糖胺浓度升高，C肽水平随年龄增加而降低，2岁时检测不到，总β细胞体积比WT减少82%。MIDY猪的血浆胰高血糖素和β-羟基丁酸水平长期升高，反映了人类糖尿病控制不良的标志。总共保存了1900份不同体液（血液、血清、血浆、尿液、脑脊液和滑液）样本以及17,000份来自150种不同组织和器官的样本，以便于进行大量的形态学和分子分析。血浆靶向代谢组学和脂质组学数据以及胰腺、肝脏和肾皮质蛋白质组谱的主成分分析清楚地分离了MIDY和WT样品。慕尼黑MIDY Pig生物样本库中广泛的定义明确的生物样本将提供给科学界，为多器官、多组学维度的糖尿病器官串扰系统研究提供了独特的资源。MIDY猪代表了人类糖尿病（DM）控制不佳的模型。采用随机系统抽样的原则，从2岁MIDY和野生型猪建立了一个复杂的生物库。血浆样品的靶向代谢组学和脂质组学分析显示MIDY和野生型猪的明显分离。慕尼黑MIDY猪生物样本库有助于在多器官、多组学维度上系统研究DM中的器官串扰。
The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences of chronic insulin insufficiency and hyperglycemia, we established a comprehensive biobank of long-term diabetic INSC94Y transgenic pigs, a model of mutant INS gene-induced diabetes of youth (MIDY), and of wild-type (WT) littermates. Female MIDY pigs (n = 4) were maintained with suboptimal insulin treatment for 2 years, together with female WT littermates (n = 5). Plasma insulin, C-peptide and glucagon levels were regularly determined using specific immunoassays. In addition, clinical chemical, targeted metabolomics, and lipidomics analyses were performed. At age 2 years, all pigs were euthanized, necropsied, and a broad spectrum of tissues was taken by systematic uniform random sampling procedures. Total beta cell volume was determined by stereological methods. A pilot proteome analysis of pancreas, liver, and kidney cortex was performed by label free proteomics. MIDY pigs had elevated fasting plasma glucose and fructosamine concentrations, C-peptide levels that decreased with age and were undetectable at 2 years, and an 82% reduced total beta cell volume compared to WT. Plasma glucagon and beta hydroxybutyrate levels of MIDY pigs were chronically elevated, reflecting hallmarks of poorly controlled diabetes in humans. In total, ∼1900 samples of different body fluids (blood, serum, plasma, urine, cerebrospinal fluid, and synovial fluid) as well as ∼17,000 samples from ∼50 different tissues and organs were preserved to facilitate a plethora of morphological and molecular analyses. Principal component analyses of plasma targeted metabolomics and lipidomics data and of proteome profiles from pancreas, liver, and kidney cortex clearly separated MIDY and WT samples. The broad spectrum of well-defined biosamples in the Munich MIDY Pig Biobank that will be available to the scientific community provides a unique resource for systematic studies of organ crosstalk in diabetes in a multi-organ, multi-omics dimension. MIDY pigs represent a model of poorly controlled diabetes mellitus (DM) in humans. A complex biobank was built from 2-year-old MIDY and wild-type pigs using the principles of random systematic sampling. Targeted metabolomics and lipidomics analyses of plasma samples revealed clear separation of MIDY and wild-type pigs. The Munich MIDY Pig Biobank facilitates systematic studies of organ crosstalk in DM in a multi-organ, multi-omics dimension.
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影响因子：
1.5
作者：
Albl, Barbara;Haesner, Serena;Blutke, Andreas
通讯作者：
Blutke, Andreas
一个自动shot弹枪脂质组学平台，用于对血浆完整脂质的高吞吐量，全面和定量分析。
DOI：
10.1002/ejlt.201500145
发表时间：
2015-10
期刊：
European journal of lipid science and technology : EJLST
影响因子：
--
作者：
Surma MA;Herzog R;Vasilj A;Klose C;Christinat N;Morin-Rivron D;Simons K;Masoodi M;Sampaio JL
通讯作者：
Sampaio JL
影响因子：
29
作者：
Stern JH;Rutkowski JM;Scherer PE
通讯作者：
Scherer PE
影响因子：
7.7
作者：
Renner S;Fehlings C;Herbach N;Hofmann A;von Waldthausen DC;Kessler B;Ulrichs K;Chodnevskaja I;Moskalenko V;Amselgruber W;Göke B;Pfeifer A;Wanke R;Wolf E
通讯作者：
Wolf E
DOI：
10.1038/nrendo.2014.171
发表时间：
2014-12
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
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