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Regulation of Beta-Cell Growth and Death

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Pancreatic Beta Cell in Health and Disease

Abstract

Pancreatic beta-cell mass, under normal circumstances, is maintained at an optimal level to provide for a normal metabolic load. It should not be viewed as static, and slow in turning over. Indeed, the adult beta-cells adults are plastic and able to increase their population to adapt to changes in metabolic demand, such as in pregnancy or nondiabetic obesity. Net changes in beta-cell mass are reflective of the amount of growth (i.e., the sum of betacell replication, neogenesis and size) minus the degree of beta-cell death (i.e., the sum of beta-cell apoptosis, necrosis and autophagic cell death). In some circumstances, such as prolonged obesity and insulin resistance, the beta-cell works under pressure trying to meet the metabolic demand, but eventually succumbs to a collective number of stresses that lead to an increase in beta-cell death, a subsequent reduction in beta-cell mass, and the eventual onset of type 2 diabetes. In this chapter, what is currently known about mechanisms of beta-cell growth and death are looked at in detail, with an emphasis on adaptive mechanisms in obesity and pregnancy and the signal transduction pathways involved in the control of beta-cell growth. Also, the various stresses on the beta cell that may lead to the onset of type 2 diabetes will be outlined and the inflammatory signaling pathways that contribute to increased beta-cell apoptosis/necrosis examined.

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Authors and Affiliations

  1. Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, 5841 S. Maryland Avenue, MC 1027, Room N138, Chicago, IL, 60637, USA

    Christopher J. Rhodes

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  1. Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Susumu Seino M.D., D.M. Sci. (Professor) (Professor)

  2. Medicine and Human Genetics, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA

    Graeme I. Bell Ph.D. (Louis Block Distinguished Service Professor) (Louis Block Distinguished Service Professor)

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Rhodes, C.J. (2008). Regulation of Beta-Cell Growth and Death. In: Seino, S., Bell, G.I. (eds) Pancreatic Beta Cell in Health and Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-75452-7_12

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