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Pancreatic Beta Cell in Health and Disease pp 381–398Cite as

Pancreatic Islet Pathology in Type 2 Diabetes

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Abstract

Inadequate insulin secretion is a major factor in type 2 diabetes. Islet dysfunction is evident at the onset of the disease but the causal factors are largely unknown; decreased beta-cell mass, as shown in rodent models of diabetes, has been proposed. Quantitative morphometry of post-mortem human pancreas has demonstrated 0–50% less beta-cell population in diabetic compared to nondiabetic subjects. The evidence for continuous turnover of beta cells in adult human pancreas by apoptosis and regeneration (as in rodents) has yet to be proven; low incidence of cell division in ducts or islets has been reported and no evidence for abnormal cell turnover contributing to decreased beta-cell mass in human diabetes has been seen. The functional capacity for increased insulin secretion is high in diabetic and nondiabetic subjects. It is likely that a deficit in function is a major contributor for type 2 diabetes in man. Islet amyloid deposition is heterogeneous in human diabetes and is unlikely to contribute to decreased beta-cell mass at onset of hyperglycemia in man as shown in rodent models, monkeys, and cats. The effects of elevated lipids on beta-cell function is mediated by modulation of metabolism but the cytotoxic effects of lipids on beta cells—lipotoxicity—is mediated largely by aberrant effects of saturated fatty acids on cells in vitro. Increased availability of human isolated islets will enable accurate determination of functional and morphological changes which contribute to impaired insulin secretion in type 2 diabetes.

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Authors and Affiliations

  1. Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LJ, UK

    Anne Clark

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  1. Anne Clark
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Editors and Affiliations

  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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© 2008 Springer

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Clark, A. (2008). Pancreatic Islet Pathology in Type 2 Diabetes. 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_18

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