Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Renner, Simone; Dobenecker, Britta; Blutke, Andreas; Zöls, Susanne; Wanke, Rüdiger; Ritzmann, Mathias; Wolf, Eckhard

doi:10.1016/j.theriogenology.2016.04.055

Cited by 57 publications

(57 citation statements)

References 176 publications

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“…Furthermore, GLUT2 through which STZ enters the cell is not only expressed in beta cells but also in liver and kidney tubular cells, resulting in dose-dependent reversible and irreversible damage in these tissues (reviewed in Ref. [8]). In contrast genetically modified MIDY pigs exhibit a stable diabetic phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…While insulin treatment restored basal insulin in MIDY pigs to the level of WT, fasting plasma levels of glucose and fructosamine, a valid parameter for the evaluation of medium-term glucose control over 2–3 weeks (reviewed in Ref. [8]), were highly elevated. These findings suggest – in accordance with observations in the Akita mouse model [23] – insulin resistance in MIDY pigs.…”

Section: Discussionmentioning

confidence: 99%

“…[8]). Transgenic pigs expressing the mutant insulin C94Y are a model for permanent neonatal diabetes [9], now termed mutant INS gene-induced diabetes of youth (MIDY) (reviewed in Ref.…”

Section: Introductionmentioning

confidence: 99%

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The Munich MIDY Pig Biobank – A unique resource for studying organ crosstalk in diabetes

Blutke¹,

Renner

Flenkenthaler³

et al. 2017

Molecular Metabolism

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ObjectiveThe 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.MethodsFemale 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.ResultsMIDY 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.ConclusionsThe 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Munich MIDY Pig Biobank – A unique resource for studying organ crosstalk in diabetes

Blutke¹,

Renner

Flenkenthaler³

et al. 2017

Molecular Metabolism

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“…The pig is another large animal model used for translational studies in research on obesity and diabetes mellitus. Obesity in pigs is routinely induced by high-energy high-fat and/or high-carbohydrate diets 331,332 . Minipig lines, such as Ossabaw, Yucatan or Göttingen minipigs, are most widely used because they can be reared to adulthood at reasonable costs.…”

Section: Large Animal Modelsmentioning

confidence: 99%

Animal models of obesity and diabetes mellitus

et al. 2018

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More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.

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“…In recent years, their use in translational research has significantly expanded due to the development of genetically modified and experimentally-induced pig models of human disease. These include cystic fibrosis 19–21 , muscular dystrophy 22 , diabetes 23 , cardiovascular disease 24,2526 , diabetes 27 , cancer 28,29 , environmental toxicology 30 , cutaneous wound healing 31 , metabolic syndrome 32 , among others. Porcine models have also been used to investigate traumatic brain injury 3 , neurodegenerative diseases 33,34 , brain development 35 , seizures 36 , cognition 37 , and neurogenesis 38 .…”

Section: Discussionmentioning

confidence: 99%

Simple and reproducible approaches for the collection of select porcine ganglia

Meyerholz

Reznikov

2017

Journal of Neuroscience Methods

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Background The anatomy and physiology of the pig nervous system is more similar to humans compared to traditional rodent models. This makes the pig an attractive model to answer questions relating to human health and disease. Yet the technical and molecular tools available to pig researchers are limited compared to rodent researchers New Method We developed simple and rapid methods to isolate the trigeminal, nodose (distal vagal), and dorsal root ganglia from neonatal pigs. We selected these ganglia due to their broad applicability to basic science researchers and clinicians Results Use of these methods resulted in reproducible isolation of all three types of ganglia as validated by histological examination. Comparison with Existing Method(s) There are currently no methods that describe a step-by-step protocol to isolate these porcine ganglia. Conclusions In conclusion, these methods for ganglia collection will facilitate and accelerate future neuroscience investigations in pig models of human disease.

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Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

Cited by 57 publications

References 176 publications

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

Animal models of obesity and diabetes mellitus

Simple and reproducible approaches for the collection of select porcine ganglia

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