Down-regulation of CASK in glucotoxicity-induced insulin dysfunction in pancreatic β cells

High-glucose level exerts deleterious effects on pancreatic beta cells, but the mechanisms remain unclear. Calcium/calmodulin-dependent serine protein kinase (CASK) plays a vital role in neural development and release of neurotransmitters, and probably plays a role in the anchoring of insulin on pancreatic beta cell membrane. Hypoxia-inducible factor 1 alpha (HIF1 alpha) is involved in beta-cell dysfunction. The aim of this study was to provide some basic evidence that CASK could be involved in glucotoxicity-induced insulin secretion dysfunction mediated by HIF1 alpha in INS-1E cells. CASK overexpression plasmid, HIF1 alpha agonist (CoCl2), and HIF1 alpha selective inhibitor (KC7F2) were used. The results showed that chronic stimulation with high glucose could induce insulin secretion dysfunction in INS-1E beta cells. Overexpression of CASK partially reversed the effects of high glucose on insulin secretion. CoCl2 reduced the expression of CASK, but KC7F2 reversed the glucotoxicity-induced CASK level reduction. These results suggested that glucotoxicity-induced insulin secretion defects in INS-1E cells could be mediated by HIF1 alpha via the down-regulation of CASK.