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Porcine models for studying complications and organ crosstalk in diabetes mellitus

Abstract

The worldwide prevalence of diabetes mellitus and obesity is rapidly increasing not only in adults but also in children and adolescents. Diabetes is associated with macrovascular complications increasing the risk for cardiovascular disease and stroke, as well as microvascular complications leading to diabetic nephropathy, retinopathy and neuropathy. Animal models are essential for studying disease mechanisms and for developing and testing diagnostic procedures and therapeutic strategies. Rodent models are most widely used but have limitations in translational research. Porcine models have the potential to bridge the gap between basic studies and clinical trials in human patients. This article provides an overview of concepts for the development of porcine models for diabetes and obesity research, with a focus on genetically engineered models. Diabetes-associated ocular, cardiovascular and renal alterations observed in diabetic pig models are summarized and their similarities with complications in diabetic patients are discussed. Systematic multi-organ biobanking of porcine models of diabetes and obesity and molecular profiling of representative tissue samples on different levels, e.g., on the transcriptome, proteome, or metabolome level, is proposed as a strategy for discovering tissue-specific pathomechanisms and their molecular key drivers using systems biology tools. This is exemplified by a recent study providing multi-omics insights into functional changes of the liver in a transgenic pig model for insulin-deficient diabetes mellitus. Collectively, these approaches will provide a better understanding of organ crosstalk in diabetes mellitus and eventually reveal new molecular targets for the prevention, early diagnosis and treatment of diabetes mellitus and its associated complications.

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Acknowledgments

The authors gratefully acknowledge Prof. Peter Cowan, Fellow of the Center for Advanced Studies (CAS) of LMU Munich, for careful editing of the manuscript.

Funding information

This work was supported by the German Center for Diabetes Research (DZD; 82DZD00802, 82DZD0043G, 82DZD0044G, 82DZD0015G to EW, SR and EK), the German Center for Cardiovascular Research (DZHK; 81X2600210, 81X2600204, 81X3600208, 81X2600249 to SC, 81Z0600207 to DM), the Deutsche Forschungsgemeinschaft (TRR127 to EW and EK and DFG DE 719/7-1/SPP2127 to CD), the European Union (iNanoBIT grant agreement no. 760986 to EK and EW), the Bayerische Forschungsstiftung (AZ-1247-16 VasOP to EK and EW), the LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative (to SC), the Förderprogramm für Forschung und Lehre (FöFöLe; 962 to SC), the Heinrich-and-Lotte-Mühlfenzl Stiftung (to SC), the ERA-NET on Cardiovascular Diseases (ERA-CVD; 01KL1910 to SC), the Netherlands Cardiovascular Research Initiative, an initiative with financial support from the Dutch Heart Foundation (CVON2014-11, RECONNECT to DM), and the Corona-Foundation (S199/10079/2019 to SC).

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Correspondence to Eckhard Wolf.

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Renner, S., Blutke, A., Clauss, S. et al. Porcine models for studying complications and organ crosstalk in diabetes mellitus. Cell Tissue Res (2020). https://doi.org/10.1007/s00441-019-03158-9

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Keywords

  • Pig model
  • Diabetes
  • Complications
  • Retinopathy
  • Cardiomyopathy
  • Nephropathy
  • Organ crosstalk
  • Biobank
  • Multi-omics analysis
  • Obesity