Ontology highlight
ABSTRACT: 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.
SUBMITTER: Blutke A
PROVIDER: S-EPMC5518720 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Blutke Andreas A Renner Simone S Flenkenthaler Florian F Backman Mattias M Haesner Serena S Kemter Elisabeth E Ländström Erik E Braun-Reichhart Christina C Albl Barbara B Streckel Elisabeth E Rathkolb Birgit B Prehn Cornelia C Palladini Alessandra A Grzybek Michal M Krebs Stefan S Bauersachs Stefan S Bähr Andrea A Brühschwein Andreas A Deeg Cornelia A CA De Monte Erica E Dmochewitz Michaela M Eberle Caroline C Emrich Daniela D Fux Robert R Groth Frauke F Gumbert Sophie S Heitmann Antonia A Hinrichs Arne A Keßler Barbara B Kurome Mayuko M Leipig-Rudolph Miriam M Matiasek Kaspar K Öztürk Hazal H Otzdorff Christiane C Reichenbach Myriam M Reichenbach Horst Dieter HD Rieger Alexandra A Rieseberg Birte B Rosati Marco M Saucedo Manuel Nicolas MN Schleicher Anna A Schneider Marlon R MR Simmet Kilian K Steinmetz Judith J Übel Nicole N Zehetmaier Patrizia P Jung Andreas A Adamski Jerzy J Coskun Ünal Ü Hrabě de Angelis Martin M Simmet Christian C Ritzmann Mathias M Meyer-Lindenberg Andrea A Blum Helmut H Arnold Georg J GJ Fröhlich Thomas T Wanke Rüdiger R Wolf Eckhard E
Molecular metabolism 20170613 8
<h4>Objective</h4>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 <i>INS</i><sup>C94Y</sup> transgenic pigs, a model of mutant <i>INS</i> gene-induced diabetes of youth (MIDY), and of wild-type (WT) littermates.<h4>Methods</h4>Female MIDY pigs (n = 4) were maintained with suboptimal insulin treat ...[more]