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Study of Dysfunction of Insulin Secretion in Islet βCells During Endoxemia in Rats

ObjectiveTo explore the effect of endotoxin on insulin secretion from islet βcell of rat pancreas.MethodsAfter the model of endotoxemia was established in rats with intraperitoneal injection of LPS (2 mg/kg),the changes of insulin level in the serum and pancreas were dynamically determined, the expression of inducible nitric oxide synthase (iNOS) by situ hybridization and DNA damage in islet cells were also observed, the effect of sodium nitroprusside (exogenous NO) on synthesis and secretion of insulin from isolated islet βcell of normal rat pancreas under high glucose stimulation was also evaluated.ResultsThe level of glucose and insulin in plasma were significantly increased at 12th and 6th h, respectively and kept on 3 d after injection of LPS,but the insulin level in pancreas was not remarkably altered.The expression of iNOS and DNA damaged significantly enhanced at 6 d after endotoxemia. The high glucosestimulated insulin synthesis and secretion were bly inhibited by exogenous NO.ConclusionThese findings suggest that LPS be stimulate the expression of iNOS and NO product,which inhibites synthesis and secretion of insulin in islet βcells,but it stimulates insulin secretion by another mechanism,and results in dysfunction and destruction of the rat pancreas.