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Integrating the inputs that shape pancreatic islet hormone release

Nature Metabolism volume 1, pages 1189–1201 (2019)Cite this article

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Abstract

The pancreatic islet is a complex mini organ composed of a variety of endocrine cells and their support cells, which together tightly control blood glucose homeostasis. Changes in glucose concentration are commonly regarded as the chief signal controlling insulin-secreting beta cells, glucagon-secreting alpha cells and somatostatin-secreting delta cells. However, each of these cell types is highly responsive to a multitude of endocrine, paracrine, nutritional and neural inputs, which collectively shape the final endocrine output of the islet. Here, we review the principal inputs for each islet-cell type and the physiological circumstances in which these signals arise, through the prism of the insights generated by the transcriptomes of each of the major endocrine-cell types. A comprehensive integration of the factors that influence blood glucose homeostasis is essential to successfully improve therapeutic strategies for better diabetes management.

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Fig. 1: Comparative architecture of pancreatic islets of mice and humans.
Fig. 2: Inter-organ signalling from nutrient sensing to islet-mediated metabolic effects.
Fig. 3: Visualization of the abundance and selectivity of GPCR and transporter gene expression in alpha, beta and delta cells.
Fig. 4: Diabetes disrupts the extensive paracrine signalling network of the islet.

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Data availability

The dataset analysed in this study are available from the Gene Expression Omnibus repository under accession number GSE90766.

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Acknowledgements

Work discussed in this Review was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-110276), the American Diabetes Association (1-19-IBS-078) and the Juvenile Diabetes Research Foundation (2-SRA-2019-700-S-B). G.M.N. was supported by a NIGMS-funded Pharmacology Training Program (T32GM099608). We thank A. Mawla for assistance in bioinformatics analysis and data presentation and T. van der Meulen for critical reading of the manuscript.

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  1. Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, Davis, CA, USA

    Glyn M. Noguchi & Mark O. Huising

  2. Department of Physiology & Membrane Biology, School of Medicine, University of California, Davis, Davis, CA, USA

    Mark O. Huising

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G.M.N. wrote the article together with M.O.H.

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M.O.H. receives funding from Crinetics Inc. to study somatostatin analogues. None of that work is discussed in this Review.

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Noguchi, G.M., Huising, M.O. Integrating the inputs that shape pancreatic islet hormone release. Nat Metab 1, 1189–1201 (2019). https://doi.org/10.1038/s42255-019-0148-2

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