Role Of Serotonin In Regulation Of Pancreatic And Mesenteric Arterial Function In Diabetic Mice

Aim:Diabetes(DM)is a common clinical endocrine disease showing the disorder of sugar metabolic.There are many complications,while one of the most serious complications is the vascular lesion of the patients.This study is mainly to investigate the response of pancreas and mesenteric artery towards 5-HT stimuli and the underlying mechanism of the nitric oxide(NO)under the giving condition of diabetes.Methods:Totally,60 male C57B1/6 mice,about 12 weeks,weight 25 to 27 grams,were randomly divided into either the control group(C57B1)or the diabetic group(DM).Diabetic mice were induced by streptozotocin(80 mg/kg/d)through intraperitoneal injection for 4 consecutive days.C57B1 mice were used as control.1.By using myograph to measure the vascular tone of the pancreas and mesenteric artery from both diabetic group and control group,5-HT and Ang II induced vascular effect were measured.2.By using myograph to measure the vascular tone of the pancreas and mesenteric artery from diabetic group and control group,5-HT2A receptor agonist DOI,5-HT1B/1D receptor agonist Sumatriptan and 5-HT2B receptor agonist BW723C86 induced vascular effect were measured.3.By using myograph to measure the vascular tone of the pancreas and mesenteric artery from diabetic group and control group,eNOS inhibitor L-NAME was used to pretreat with the vessels,and then 5-HT induced vascular effect were measured.4.By using myograph to measure the vascular tone of the pancreas and mesenteric artery from diabetic group and control group,NE was used to pretreat with the vessels,and then SNP induced vascular effect were measured.5.Real-time PCR was used to measure the mRNA levels of eNOS?5-HT1B?5-HT1D?5-HT2A?5-HT2B in pancreas and mesenteric artery from both diabetic group and control group.6.ELISA was used to measure the concentration of 5-HT in blood plasma and eNOS in pancreas and mesenteric artery from both diabetic group and control group.Results:1.The concentration of 5-HT in plasma was significantly higher in diabetic group than which in control group.2.Pancreas and mesenteric artery isolated from diabetic mice had impaired contractions to 5-HT,showing no difference from Ang II treatment.3.Pancreas and mesenteric artery isolated from diabetic mice had impaired contractions to DOI,Sumatriptan and BW723C86.4.Pancreas and mesenteric artery isolated from diabetic mice had impaired contractions to 5-HT that were normalized by incubation with L-NAME.5.Pancreas and mesenteric artery isolated from both diabetic group and control group showed no difference to SNP after pretreated with NE.6.The mRNA level of eNOS and 5-HT receptor(5-HT1B?5-HTlD?5-HT2A?5-HT2B)in pancreas and mesenteric artery showed no difference between control group and diabetic group.7.The concentration of eNOS in pancreas and mesenteric artery showed reduce tendency in diabetic group;however there was no significant difference between the diabetic group and control group.Conclusion:The responses of pancreas and mesenteric artery to 5-HT decreased under the giving condition of diabetes.It may due to the decreased activity of 5-HT receptors and the activation of eNOS,which releases nitric oxide more and makes the vessels contract less.