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The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes
- Source :
- Molecular Metabolism, Mol. Metab. 6, 931-940 (2017), Molecular Metabolism, 6 (8), Molecular Metabolism, Vol 6, Iss 8, Pp 931-940 (2017)
- Publication Year :
- 2017
- Publisher :
- ETH Zurich, 2017.
-
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.<br />Molecular Metabolism, 6 (8)
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism, Mol. Metab. 6, 931-940 (2017), Molecular Metabolism, 6 (8), Molecular Metabolism, Vol 6, Iss 8, Pp 931-940 (2017)
- Accession number :
- edsair.doi.dedup.....88b1481c9a2871b73b2f44f0fbd847be
- Full Text :
- https://doi.org/10.3929/ethz-b-000191775