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Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
  • Published:
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Abstract

Islets of Langerhans contain multiple hormone-producing endocrine cells controlling glucose homeostasis. Transcription establishes and maintains islet cellular fates and identities. Genetic and environmental disruption of islet transcription triggers cellular dysfunction and disease. Early transcriptional regulation studies of specific islet genes, including insulin (INS) and the transcription factor PDX1, identified the first cis-regulatory DNA sequences and trans-acting factors governing islet function. Here, we review how human islet “omics” studies are reshaping our understanding of transcriptional regulation in islet (dys)function and diabetes. First, we highlight the expansion of islet transcript number, form, and function and of DNA transcriptional regulatory elements controlling their production. Next, we cover islet transcriptional effects of genetic and environmental perturbation. Finally, we discuss how these studies’ emerging insights should empower our diabetes research community to build mechanistic understanding of diabetes pathophysiology and to equip clinicians with tailored, precision medicine options to prevent and treat islet dysfunction and diabetes.

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Acknowledgments

We apologize to colleagues whose work was not directly cited due to reference limitations. We thank Jesse Hammer in JAX Graphics Design and Production Services for the figure artwork. We would like to thank our colleagues at JAX-GM (Adam Williams), University of Michigan (Stephen C. J. Parker), and the National Human Genome Research Institute (Lori Bonnycastle and Brooke Wolford) for their helpful suggestions and critical review of this manuscript. This work was supported by US National Institutes of Health (NIH) grant R00DK092251-03 to M.L.S.

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Michael L. Stitzel, Ina Kycia, Romy Kursawe, and Duygu Ucar declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. The Jackson Laboratory for Genomic Medicine (JAX-GM), Farmington, CT, USA

    Michael L. Stitzel, Ina Kycia, Romy Kursawe & Duygu Ucar

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  1. Michael L. Stitzel
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  2. Ina Kycia
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Correspondence to Michael L. Stitzel.

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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

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Stitzel, M.L., Kycia, I., Kursawe, R. et al. Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function. Curr Diab Rep 15, 66 (2015). https://doi.org/10.1007/s11892-015-0635-0

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