Aims/hypothesis: Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential.
Methods: Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied.
Results: In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38.
Conclusion/interpretation: These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.