ABSTRACT
Objective To explore the effects of DPP-4 inhibitor sitagliptin on insulitis of NOD mice and the potential mechanism. Methods 223-month-old female NOD mice were randomly divided into Sitagliptin(Si-ta)group(n=11)gavaged with Sita(30 mg/Kg)daily for 12 weeks and control(Con)group with equal volume of normal saline(NS). The body weight,food-intake,water-intake and blood glucose were recorded weekly. Intraperi-toneal glucose tolerance test(IPGTT)was performed at the end of treatment and the blood sample was collected. Then mice were execute. The serum insulin level was measured by ELISA. Pancreas morphology and insulitis were evaluated by hematoxylin-eosin staining. The protein expression level of TLR4 ,MyD88 and NF-κB was analyzed by Western Blot. Results Compared with that of Con group ,the insulitis of Sita group was significantly alleviative(P < 0.05)and the serum insulin level was increased significantly(P < 0.05). The protein expression level of TLR4(P<0.05),MyD88(P<0.01)and NF-κB(P<0.05)in Sita group was significantly decreased. Conclusion Sitagliptin alleviates insulitis in NOD mice and increases the serum insulin level ,probably owing to the suppression of TLR4/MyD88/NF-κB signaling pathway.
ABSTRACT
Objective To explore the effects of DPP-4 inhibitor sitagliptin on insulitis of NOD mice and the potential mechanism. Methods 223-month-old female NOD mice were randomly divided into Sitagliptin(Si-ta)group(n=11)gavaged with Sita(30 mg/Kg)daily for 12 weeks and control(Con)group with equal volume of normal saline(NS). The body weight,food-intake,water-intake and blood glucose were recorded weekly. Intraperi-toneal glucose tolerance test(IPGTT)was performed at the end of treatment and the blood sample was collected. Then mice were execute. The serum insulin level was measured by ELISA. Pancreas morphology and insulitis were evaluated by hematoxylin-eosin staining. The protein expression level of TLR4 ,MyD88 and NF-κB was analyzed by Western Blot. Results Compared with that of Con group ,the insulitis of Sita group was significantly alleviative(P < 0.05)and the serum insulin level was increased significantly(P < 0.05). The protein expression level of TLR4(P<0.05),MyD88(P<0.01)and NF-κB(P<0.05)in Sita group was significantly decreased. Conclusion Sitagliptin alleviates insulitis in NOD mice and increases the serum insulin level ,probably owing to the suppression of TLR4/MyD88/NF-κB signaling pathway.
ABSTRACT
0.05). The main toxicities were well tolerated and consisted of leukopenia,nausea/vomiting and peripheral neuritis. Grades Ⅲ-Ⅳ nausea/vomiting,renal toxicity and cardiac insufficiency occurred more frequently in the control group,peripheral neuritis occurred more frequently in the study group (P