Valproic acid does not affect decreased insulin secretion in WFS1‐deficient pancreatic islets

Abstract

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile‐onset diabetes mellitus and optic atrophy, is caused by mutations in the wolframin (WFS1) gene. WFS1 negatively regulates endoplasmic reticulum (ER) stress signalling and therefore have a role in the pathogenesis of diabetes. Valproic acid (VPA), a widely used anticonvulsant and mood‐stabilizing drug, normalized the glucose intolerance in Wfs1 mutant mice, but had no effect on the course of glucose tolerance in wild‐type (WT) mice. The aim of this study was to investigate insulin secretion in isolated pancreatic islets of WFS1‐deficient (Wfs1KO) mice and also evaluate insulin secretion in the presence of VPA. In addition, the content of proinsulin in the isolated islets was measured. In general Wfs1KO pancreatic islets secreted less insulin compared to WT and Wfs1HZ islets. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KO had an increased level of proinsulin. We found significantly reduced insulin secretion in Wfs1 mutants and no effect of VPA treatment.This study was supported by the Frontiers of Functional Genomics and by The European Regional Development Fund.