Dipeptidyl Peptidase-4 Inhibitor Protects Against Renal Damage in Renal Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats
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Dipeptidyl Peptidase-4 Inhibitor Protects Against Renal Damage in Renal Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats, LAILA A. EL-SAYED, SAMAH EL-ATTAR and LAILA RASHED
Abstract
Background: Glucagon-like peptide-1 (GLP-1) is a hor-mone secreted by intestinal L cells. It is the most potent stimulator of glucose-induced insulin secretion. The incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), is attenuated in T2DM. Native GLP-1 has a short half-life, being degraded by dipeptidyl peptidase-4 (DPP-4), it is necessary to use a DPP-4 inhibitor to prevent its degradation.
Aim: The aim is to investigate the effect of DPP-4 inhibitor on renal injury induced by renal I/R in streptozotocin induced diabetic rats.
Design: Seventy male albino rats were divided into 7 groups, group 1- normal control, group 2- renal IR injury, group 3- DPP-4 inhibitor treatment in a dose of 10mg/kg BW for 6 weeks + renal IR injury, group 4- diabetic rats, group 5- diabetic rats + DPP-4 inhibitor, group 6- diabetic rats + renal IR injury and group 7- diabetic rats + DPP-4 inhibitor treatment + renal IR injury. In all the included animals, urea and creatinine, fasting blood glucose level, insulin level and insulin resistance test were evaluated. Oxidant stress was evaluated by measuring tissue MDA, glutathione and nitrite level. The inflammatory marker TNFa and MPO activity and DNA fragmentation were measured in the renal tissues.
Results: DPP-4 treatment improved blood glucose level, insulin and insulin sensitivity as compared to diabetic rats. MDA and nitrite levels in the renal tissue were significantly increased and glutathione was significantly decreased after I/R in diabetic rats compared to I/R in normal rats. DPP-4 inhibitor treatment significantly normalized these biochemical parameters. TNFa level, MPO activity was reduced in DPP-4 inhibitor treated I/R diabetic rats as compared to untreated group. DNA fragmentation was attenuated in the DPP-4 inhibitor treated groups compared to untreated rats. Moreover, DPP-4 inhibitor treatment preserved the function of the kidney after exposure to I/R injury.
Conclusion: This study proved that DPP-4 inhibitor protected diabetic rat kidneys from being damaged due to I/R injury through improving the glycemic states, attenuating oxidative stress, reducing inflammation, apoptosis and may be through a direct effect on the renal tissues.