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Preservation of β-cell function

There is growing evidence that progressive β-cell dysfunction is crucial
for the development and progression of T2DM, 67 68 the exact nature of
which is still not fully understood, although several β-cell “aggressors”
have been identified (Figure 5). In patients with T2DM it has been ob-
69
served there is a reduced islet number and/or diminished β-cell mass
in the pancreas due to increased apoptosis and inadequate regen-
eration. β-cells are known to have a very low antioxidant capacity,
70
which has the potential to render them vulnerable to oxidative stress
by reactive oxygen and nitrogen species. This process is believed to
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be central in the impairment of β-cell function during the development
of T2DM. 71

Although T2DM is associated with a progressive decline in β-cell func-
tion, it has been shown that certain pharmacological treatments, such
as DPP-4 inhibitors, metformin and TZDs can ameliorate β-cell func-
tion. 72-74 In-vivo studies, usually performed in young rodents, have dem-
onstrated that DPP-4 inhibitors exhibit favourable actions on islet and
β-cell mass, morphology, and survival. 74 75 Since similar beneficial effects
were not observed with sulphonylurea treatment, it is believed that the
effects on insulin-secreting cells in these in-vivo studies are mediated
through specific actions of the drug(s) directly on β-cells rather than by
an improvement of the metabolic milieu. 76

Figure 5: Proposed model for the interplay between “aggressors” of the beta-cell in the
pathogenesis of T2DM. 69

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