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

Yen Ta Chen, Christopher Glenn Wallace, Chih Chao Yang, Chih Hung Chen, Kuan Hung Chen, Pei Hsun Sung, Yung Lung Chen, Han Tan Chai, Sheng Ying Chung, Sarah Chua, Fan Yen Lee, Sheung Fat Ko, Mel S. Lee, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

22 Scopus citations

Abstract

We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIRextendin- 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-DPP4D rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4D 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-DPP4D rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIRDPP4D 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.

Original languageEnglish
Pages (from-to)54821-54837
Number of pages17
JournalOncotarget
Volume8
Issue number33
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© Chen et al.

Keywords

  • Acute kidney ischemia-reperfusion injury
  • Dipeptidyl peptidase 4 deficiency
  • Inflammation
  • Oxidative stress
  • Preconditioning

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