Mechanism Of Rosiglitazone On The Regulation Of The Oligopeptide Transporter PepT1 Expressionin Jejunum Of Septic Rat

Objective:The aim of this study was to investigate the oligopeptide transporter (PepTl) expression during cecal ligation and puncture(CLP) model and the effect of rosiglitazone pretreatment on PepTl expression.Methods:The SD rats were randomly divided into CLP+vehicle,C group; sham+vehicle,S group; CLP+rosiglitazone,R group; CLP+rosiglitazone+insulin, RI group; CLP+insulin,CI group; normal, N group. C,S group rats received 0.9% NaCl solution by intragastric administration at 30 min before CLP or sham operation,while R group received rosiglitazone (by intragastric administration at 30 min before CLP).RI and CI group received insulin injected through femoral vein at 152min after CLP.N group received no administration. the glucose was measured at 30min preoperatively and every 30min postoperatively.At 155min, artery blood was withdrawed for plasma TNF-a levels.The proximal jejunum was excised and jejunum TNF-a levels were also measured. Intestinal histological analysis and Immunohistochemistry for insulin receptor were investigated at determinate time.In addition, IR-βProtein, total protein and tyrosine phosphorylation levels of IRS-1 were analyzed. Peptl expression was also investigated at determinate time.Results:1. Rosiglitazone decreased RR, WBC. Plasma glucose concentrations in was significantly higher following CLP, specially at 30min,60min postoperatively than that in S, R, N group(p<0.01) Rosiglitazone significantly decreased maximum,60min glucose and fluctuation of glucose postoperatively. Plasma insulin concentration in C group was higher than that in R group(P<.01 vs R group). Rosiglitazone significantly decreased HOMA-IRI(P<.01 vs C group), production of TNF-a in plasma(P <.01 vs C group).2. Rosiglitazone significantly decreased production of TNF-a in plasma and jejunum. no significant differences were observed between groups about intestine mucosal injury and inflammation. The presence of IR-βsubunits distributed on both endoluminal. Rosiglitazone decreased basic IR-βprotein expression(P<.01 vs C). rosiglitazone increased baseline in R group(P<.05 vs C)and insulin-induced Tyr phosphorylation of IRS-1 in RI group(P<.01 vs C).No significant differences from total protein of IRS-1 between each groups(p>.05).3. CLP decreased PepTl expression, rosiglitazone pretreatment increased PepTl expression in baseline and insulin-induced PepTl expression.Conclusion:CLP induced insulin resistance at early phase, rosiglitazone pretreatment helped low hyperglycemia and decreased insulin resistance and production of inflammatory cytokine. No significant differences were observed about intestine mucosal injury and inflammation between groups at early phase,but intestinal insulin signaling was impaired:Insulin receptor substrate-1 tyrosine phosphorylation is decreased,the expression of the insulin receptor is increased in intestine of CLP rats. Rosiglitazone pretreatment helped low systematic and local production of TNF-a and increase IRS-1 tyrosine phosphorylation, decrease IR-P protein in intestine. CLP decreased PepTl expression in the rat Jejunum. Rosiglitazone pretreatment inhibited this effect.