<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Spontaneous diabetes in the NOD mouse can be
prevented by nicotinamide or by an infant formula
diet in which the protein source is replaced with
casein hydrolysate (Pregestimil) or soy protein
(Prosobee). NOD mice maintained on the standard
diet (chow and water) and given cyclophosphamide
(Cy) at day 95 develop accelerated and synchronised
diabetes within 14 days. Here, we compared the
ability of oral nicotinamide or Prosobee, either given
alone or concurrently, from weaning, in preventing
diabetes in the Cy model. The resulting insulitis and
the expression of intra-islet inducible nitric oxide
synthase (iNOS) were examined at days 0, 4, 7, 11
and 14 following Cy administration. Intra-islet CD4
and CD8 cells and macrophages were also enumerated
at day 11. In mice given the standard diet and
injected with Cy at day 95 (group 5), diabetes
developed in 7/11 mice, 14 days later. Mice exposed
to oral nicotinamide (group 2), Prosobee (group 3) or
both (group 4), did not develop the disease during
this period and until a further 30 days (<italic>p</italic> =  0.03). In
mice exposed to the standard diet and without Cy
treatment (group 1) the insulitis scores increased
slowly until day 11 and then declined slightly at day
14 whereas mice exposed to the same diet but given
Cy at day 95, showed a sharp decline at day 4
followed by a rapid increase between day 7–14.
However, in mice given either nicotinamide, Prosobee
or both, the insulitis scores at most time-points
were generally lower than in Cy-teated animals on
the standard diet. In the latter group, CD4 and CD8
cells and macrophages were also higher at day 11
than all other 4 groups (CD4: <italic>p</italic> &lt; 0.05; CD8: <italic>p</italic> &lt; 0.05;
macrophages: <italic>p</italic> &lt; 0.0001). The number of iNOS
labelled cells increased progressively in mice on
the standard diet and given Cy and were significantly
higher at days 4, 7 and 11 than in the 3 dietary
groups. Thus, oral nicotinamide or Prosobee, either
alone or together, prevents Cy induced diabetes in
the NOD mouse. The protective diets suppress Cyinduced
intra-islet immune cell influx and iNOS
expression.</p>
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Int J Exp Diabetes Res. 2000; 1(4):299-313