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IGF-1 and Insulin-Receptor Signalling in Insulin-Secreting Cells: From Function to Survival

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Abstract

Insulin and insulin-like growth factor 1 (IGF-1) receptors are ubiquitously expressed and regulate cell growth, survival, and function. In insulin-secreting cells, they contribute to proper insulin synthesis and secretion, as well as to overall pancreatic β-cell survival. The most convincing proof of the importance of these signalling pathways came from mice deficient in insulin receptors, IGF-1 receptors, or insulin receptor substrate-2 (IRS-2). Knockout of the insulin receptor or IRS-2 leads to life-threatening hyperglycemia and is prevented by β-cell-specific expression of IRS-2. Pancreatic β-cells exist in an insulin-rich environment, and therefore, the regulation and activation of their receptors must differ from cells in peripheral insulin-sensitive tissues. Intriguingly, the downstream signalling of these receptors diverges towards anti- and proapoptotic pathways: receptor activation improves cell function and growth but also induces feedback inhibition and apoptosis. This chapter summarizes current understanding of insulin and IGF-1 receptor regulation; signalling and function in β-cells with special emphasis on the regulation of insulin receptor substrates, IRS-1 and IRS-2; downstream kinases; and feedback mechanisms that impair β-cell function.

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  1. Department of Internal Medicine, Clinical Chemistry and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany

    Susanne Ullrich

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    Md. Shahidul Islam

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Ullrich, S. (2015). IGF-1 and Insulin-Receptor Signalling in Insulin-Secreting Cells: From Function to Survival. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_26

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