Effects of diazinon on the activity and gene expression of mitochondrial glutamate dehydrogenase from rat pancreatic Langerhans islets

The main propose of the present study was to determine the effects of diazinon on the activity and gene expression of glutamate dehydrogenase (GDH) as the key enzyme of Langerhans islet for secretion of insulin. Diazinon was administered intraperitoneally at doses of 15, 30, and 60 mg/kg. Langerhans islets were isolated from the pancreas of rats by a standard collagenase digestion, separation by centrifugation, and hand-picking technique. The activity and gene expression of the mitochondrial GDH was determined in the islets homogenates. Glutamate, C-peptide, and insulin were determined in plasma. Diazinon at all tested doses (15, 30, and 60 mg/kg) significantly (p < 0.01) decreased plasma insulin after 1 h while the values did not differ from control when examined after 18 h. Diazinon at all tested doses (15, 30, and 60 mg/kg) significantly (p < 0.01) increased concentration of C-peptide both 1 and 18 h post-administration. Diazinon at all tested doses (15, 30. and 60 mg/kg) significantly (p < 0.05) increased production of glutamate while the values did not differ from control when tested after 18 h. Administration of diazinon at doses of 30 and 60 mg/kg significantly (p < 0.001) increased activity of GDH after 1 h while all doses of diazinon increased GDH activity when measured after 18 h. Diazinon at dose of 60 mg/kg significantly (p < 0.01) decreased expression of GDH gene 18 h post-administration. It is concluded that GDH is a component of diazinon-induced changes in release of improper insulin. (C) 2008 Elsevier Inc. All rights reserved.