The Role Of Sitagliptin On Endoplasmic Reticulum Stress In Pancreatic Beta Cell Of Diabetic Rats

Objective：To observe the role of Sitagliptin (Sita) on endoplasmic reticulum stress in pancreaticbeta cell of diabetes rats.Methods:Fourty Sprague Dawley (SD) rats were divided into normal diets group (NC group,n=10) and high sucrose-fat diets group (HSFD group, n=30). NC group was fed withstandard chow, while HSFD group was fed with high sucrose-fat diets (HSFDs).8weeks later, the subjects in HSFD group were injected intraperitoneally with dosestreptozotocin (STZ,30mg/kg) while those in NC group were injectedintraperitoneally with a similar dose of normal saline. Subjects with FBG higher than16.7mmol/L in three consecutive days were successfully modeled. Then they weregrouped into untreated diabetes control group (DM group, n=10) and Sitagliptintreated group (Sita group, Sita100mg/kg·d, n=10). NC group and DM group weregavaged equal physiological saline. Body weight and FBG were measured after0,4,8,12,16,20weeks respectively, intraperitoneal glucose tolerance test (IPGTT) andinsulin tolerance test (ITT) were conducted before and after Sitagliptin treated for20weeks, and FINS, TG, TC, LDL-C, HDL-C were measured after20weeks. Theexpression of insulin secretion related gene PDX-1and endoplasmic reticulum stressrelated gene ERp46, CHOP, JNK, casepase12mRNA and protein were detected byreverse transcriptase-polymerase chain reaction (RT-PCR) and western blotrespectively.Results:1）After Sitagliptin treatment for8weeks, FBG in Sita group was lower evidently thanthat in DM group （P<0.05）and body weight in Sita group has no significantdifference with that in DM group (P>0.05). 2）After Sitagliptin intervention for20weeks, FBG and AUC of IPGTT and ITT inSita group decreased obviously（P<0.05) compared with DM group, while FINSincreased significantly (P<0.05). However, body weight and TG, TC, LDL-C, HDL-Chas no significant difference (P>0.05).3）The expression of PDX-1, ERp46mRNA and protein in DM group decreasedobviously (P<0.05), but increased significantly in Sita group (P<0.05). Conversely,the expression of CHOP, Caspase12, JNK in DM group increased obviously (P<0.05),while decreased significantly in Sita group (P<0.05).Conclusions:1）The FBG is effectively decreased and plasma insulin increased significantly withSitagliptin treated in HSFDs/STZ-induced diabetes rats, while no significance existsin the effect of body weight.2）The expression of PDX-1in beta cell of HSFDs/STZ-induced diabetes ratsdecreases, while the ERS in beta cell increases, which suggests that ERS mayparticipate in the progress of beta cell dysfunction in diabetic rats.3）Sitagliptin may protect the function of beta cell through down-regulating ERS ofbeta cell in diabetes rats.