Pancreatic Islet Pathology in Type 2 Diabetes

  • Anne Clark


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.


Insulin Secretion Beta Cell Islet Cell Nondiabetic Subject Islet Amyloid Polypeptide 
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© Springer 2008

Authors and Affiliations

  • Anne Clark
    • 1
  1. 1.Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and MetabolismChurchill HospitalOxfordUK

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