1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...

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augmentation. Obviously, diminished proliferation or increased apoptosis or both will
result in lower beta-cell mass. There is evidence that increased beta-cell apoptosis in the
Zucker diabetic fatty rat (ZDF), an animal model of DM2, underlies the decreased beta-cell
mass seen in these animals (34). Autopsy data examining beta-cell mass in obese and
diabetic humans have been sparce and sometimes contradictory. It is difficult to distinguish
between the two mechanisms, cell formation and cell death, in human tissue sections
mainly because dead cells are removed rapidly from the islet by macrophages and
neighbouring cells, making it hard to quantify cells death. Although cell proliferation can
be quantified in tissue sections using markers, this only provides a single snapshot in time
which probably does not reflect accurately the complex dynamic of the process (21).
Recently, the study by Butler and colab (4), as mentioned in the Introduction, showed
relative beta-cell volume to be increased by 50% in obese compared to lean non-diabetics
pancreas and was attributed to increased neogenesis of islets from exocrine ductal tissue.
Relative beta-cell volume was decreased in obese IGT and more in obese DM2 compared
to nondiabetic controls being attributable to accelerated cell apoptosis. Other studies (35,
36) have also shown a reduction in beta-cell mass in DM2, leading to a rapid emphasis of
this etiological factor.
Potential mechanisms of beta-cell adaptation can be summarized as follows (37) :
• Functional up and down-regulation of secretory machinery
• Beta-cell recruitment
• Beta-cell turnover and islet mass changes
(Evidence mainly from rodent work)
Increasing/decreasing cell size
β-cell turnover
de-novo differentiation (neogenesis) of beta-cells within
islets and new islets budding from exocrine acinar cell
pancreas
β-cell death by necrosis vs. apoptosis (programmed β-cell
death)