The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes
| Autor: | Sophie Gumbert, C. Otzdorff, Stefan Bauersachs, Jerzy Adamski, Barbara Albl, Marco Rosati, Alessandra Palladini, Eckhard Wolf, Andreas Jung, Kaspar Matiasek, Mattias Backman, Birte Rieseberg, Arne Hinrichs, Mathias Ritzmann, Miriam Leipig-Rudolph, Kilian Simmet, Caroline Eberle, Manuel Nicolas Saucedo, Stefan Krebs, Simone Renner, Robert Fux, Alexandra Rieger, Elisabeth Streckel, Serena Haesner, Christina Braun-Reichhart, Judith Steinmetz, Birgit Rathkolb, Christian Simmet, Ünal Coskun, Cornelia Prehn, Andreas Brühschwein, Erica De Monte, Helmut Blum, Nicole Übel, Martin Hrabě de Angelis, Andreas Blutke, Hazal Öztürk, Andrea Bähr, Frauke Groth, Florian Flenkenthaler, Elisabeth Kemter, Rüdiger Wanke, Thomas Fröhlich, Daniela Emrich, Michal Grzybek, Anna Schleicher, Cornelia A. Deeg, Michaela Dmochewitz, Mayuko Kurome, Andrea Meyer-Lindenberg, H.-D. Reichenbach, Georg J. Arnold, Antonia Heitmann, Patrizia Zehetmaier, M. Reichenbach, Marlon R. Schneider, Erik Ländström, Barbara Keßler |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Swine medicine.medical_treatment Stereology CPT1 carnitine O-palmitoyltransferase 1 Bioinformatics MIDY Random systematic sampling PC phosphatidylcholine 0302 clinical medicine Germany Insulin FFA free fatty acids Hyperglycemia Biobank Metabolomics Pig model Insulin insufficiency Transcriptomics Body Fluids Female FFA - Free fatty acids lcsh:Internal medicine TAG triacylglycerol 030209 endocrinology & metabolism Tissue Banks Brief Communication CE cholesterol ester ER endoplasmic reticulum 03 medical and health sciences Diabetes mellitus medicine Animals lcsh:RC31-1245 Molecular Biology PCA principal component analysis SM sphingomyelin business.industry Cell Biology medicine.disease WT wild-type Disease Models Animal 030104 developmental biology Diabetes Mellitus Type 2 MIDY mutant INS gene-induced diabetes of youth Insulin Insufficiency Midy Pig Model Random Systematic Sampling business |
| Zdroj: | Molecular Metabolism Mol. Metab. 6, 931-940 (2017) Molecular Metabolism, 6 (8) Molecular Metabolism, Vol 6, Iss 8, Pp 931-940 (2017) |
| DOI: | 10.3929/ethz-b-000191775 |
| Popis: | Objective 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. Methods 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. Results 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. Conclusions 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. Molecular Metabolism, 6 (8) |
| Databáze: | OpenAIRE |
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