Role of CYP2E1 in ketone-stimulated insulin release in pancreatic B-cells.

Abstract The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic β-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express the CYP2E1 isoform which was inducible by pretreatment of animals with acetone. The cDNA encoded CYP2E1 was expressed and inducible in the engineered cells as shown by Western blotting. The transfected protein was enzymatically active in the heterologous cells as determined by p -nitrophenol hydroxylation rates (0.176±0.08 vs. 0.341±0.08 nmol/min/mg microsomal protein in BRIN BD11 control cells and BRIN BD11h2E1 cells respectively, P P p -nitrophenol hydroxylation (0.968±0.09 nmol/min/mg microsomal protein, P P P P P P P P P P