DPP-4 enzyme deficiency protects kidney from acute ischemia-reperfusion injury: role for remote intermittent bowel ischemia-reperfusion preconditioning.

We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4(D)) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4(D)) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4(D), (3) KIR-F344 (4) KIR-DPP4(D), (5) DPP4(D)-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4(D) rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4(D) than KIR-F344 rats after acute KIR. KIR-F344 rats showed greater inflammation, oxidative stress, apoptosis, DNA damage and kidney injury than other rat groups. Damage to the kidney architecture in KIR-F344 rats was greater than in BIR-KIR-F344 or KIR-DPP4(D) rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIR-DPP4(D) and BIR-KIR-F344 than KIR-F344 rats, which suggests better intrinsic responses. We therefore suggest that elevated circulating GLP-1 levels due to DPP4 deficiency and BIR preconditioning protect kidney function and architecture during acute IR injury.