The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes.
Mol Metab
; 6(8): 931-940, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28752056
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, â¼1900 samples of different body fluids (blood, serum, plasma, urine, cerebrospinal fluid, and synovial fluid) as well as â¼17,000 samples from â¼50 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.Palavras-chave
Biobank; CE, cholesterol ester; CPT1, carnitine O-palmitoyltransferase 1; ER, endoplasmic reticulum; FFA, free fatty acids; Hyperglycemia; Insulin insufficiency; MIDY; MIDY, mutant INS gene-induced diabetes of youth; Metabolomics; PC, phosphatidylcholine; PCA, principal component analysis; Pig model; Proteomics; Random systematic sampling; SM, sphingomyelin; Stereology; TAG, triacylglycerol; Transcriptomics; WT, wild-type
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Suínos
/
Bancos de Tecidos
/
Líquidos Corporais
/
Diabetes Mellitus Tipo 2
/
Modelos Animais de Doenças
/
Insulina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article