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Expression study of GLUT4 translocation-related genes in a porcine pre-diabetic model

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Abstract

Obesity is a world-wide exponentially growing health problem that increases the risk of co-morbidities including metabolic syndrome, pre-diabetes, Type 2 Diabetes Mellitus (T2DM), and cancer. These co-morbidities are all complex conditions constituting a big challenge when searching for susceptibility genes. Identification of relevant genes, which could contribute to an earlier identification of individuals prone to develop diabetes, is urgently needed as many long-term complications can be avoided by preventive measures. Pre-diabetes is mainly associated with hyperglycemia; thus studying this phenotype might provide knowledge on relevant genes implicated in molecular mechanisms underlying pre-diabetes, and contributing to the development of T2DM. In the present study, two groups of pigs with high (HGG, N = 6) and low (NGG, N = 6) fasting plasma glucose level respectively were selected from a large pig population. Transcriptional levels of seven genes involved in the glucose transporter 4 (GLUT4) translocation pathway were studied by quantitative real-time PCR (qPCR) in diabetes relevant tissues (pancreas, adipose tissue, skeletal muscle, liver and kidney). Three of the genes, TBC (Tre-2, BUB2, CDC16) 1 Domain Family Member 4 (TBC1D4), insulin receptor and GLUT4 showed altered expression in some of the tissues. The expression pattern observed is in agreement with what has previously been reported in pre-diabetic humans confirming the pre-diabetic status of our pigs. Moreover, a novel isoform of TBC1D4 was detected by Western blotting using protein extracted from pancreas. The expression level of this novel isoform was further verified by qPCR in all tissues, showing the highest expression in the pancreas.

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Acknowledgments

We would like to thank Christel Ammitzböll Halberg and Minna Jakobsen for their assistance with RNA isolation and DNase treatment. We would also like to thank all the people involved in the generation, phenotypic measurements, and slaughtering of the F2 pig population. This study was supported by The Danish Independent Research Council Grant Number DFF 1335-00127.

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Authors and Affiliations

  1. Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870, Frederiksberg C, Denmark

    Thea Kristensen, Merete Fredholm & Susanna Cirera

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  1. Thea Kristensen
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  2. Merete Fredholm
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  3. Susanna Cirera
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Correspondence to Susanna Cirera.

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Kristensen, T., Fredholm, M. & Cirera, S. Expression study of GLUT4 translocation-related genes in a porcine pre-diabetic model. Mamm Genome 26, 650–657 (2015). https://doi.org/10.1007/s00335-015-9601-z

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  • DOI: https://doi.org/10.1007/s00335-015-9601-z

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