Regulation Of PDX-1 And The Consequent Effects On Insulin Synthesis

PURPOSE We study the nutrient and hormonal regulation of PDX-1 expression and insulin synthesis, so as to reveal the effects that PDX-1 expression has on insulin synthesis and its possible mechanism.METHOD Islet cells isolated from Sprague-Dawley (SD) rats were incubated in mediums containing 5.6 mmol/L and 33 mmol/L glucose respectively for 3 days, and in 20 nmol/L dexamethosone, and 0.6 mmol/L palmitate respectively for 3 days. Basic and glucose-induced insulin release as well as the insulin content in islet cells were detected by radio inmmuno assay (RIA). The PDX-1 protein expression was detected using inmmunochemistry assay. The PDX-1 mRNA expression was determined by in situ hybridization.RESULT 1) Islet cells exposed to 33 mmol/L glucose showed dramatic decreases in the basic and glucose-induced insulin release , cell insulin cotent and in PDX-1 protein expression ( P < 0.01 ). The PDX-1 mRNA expression in islet cells exposed to different concentration of glucose appeared to be of no significant changes ( P > 0.05 ). 2) Islet cells exposed to 20 nmol/L dexamethosone showed dramatic decreases in the basic and glucose-induced insulin release, cell insulin cotent, PDX-1 protein expression and in PDX-1 mRNA expression ( P < 0.01 ). 3) islet cells exposed to 0.6 mmol/L palmitate alonged with 5.6 mmol/L glucose showed dramatic decreases in the basic and glucose-induced insulin release , cell insulin cotent , PDX-1 protein expression as well as the PDX-1 mRNA expression ( P < 0.01 ). 4) PDX-1 protein expression is correlated with each stage of insulin synthesis ( P < 0.01 ), which showed that PDX-1 protein expression had a dramatic effect on insulin synthesis.CONCLUSION PDX-1 protein expression is a key factor in insulin synthesis. Exposure of islet cells to high concentration of glucose, dexamethosone and palmitate can reduce the expression of PDX-1, therefore affects the insulin synthesis of islet cells.