Dietary zinc restriction promotes degeneration of the endocrine pancreas in mice

Zinc is a key component of several proteins, interacting with the pancreatic hormones insulin and amylin. The role of zinc in insulin oligomerization and crystallinity is well established, although the effects of dietary zinc restriction on both energetic metabolism and beta-pancreatic hormonemia and morphology remain unexplored. Here we report the effects of dietary zinc restriction on the endocrine pancreas and metabolic phenotype of mice. Nontransgenic male Swiss mice were fed a low-zinc or control diet for 4 weeks after weanling. Growth, glycemia, insulinemia and amylinemia were lower and pancreatic islets were smaller in the intervention group despite the preserved insulin crystallinity in secretory granules. We found strong immunostaining for insulin, amylin and oligomers in apoptotic pancreatic islet. High production of beta-pancreatic hormones in zinc-restricted animals counteracted the reduced islet size caused by apoptosis. These data suggest that zinc deficiency is sufficient to promote islet beta-cell hormonal disruption and degeneration.