Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat

Yang, Hua; Li, Heng; Wang, Zhendi; Shi, Yihai; Jiang, Guosong; Zeng, Fuqing

doi:10.1016/j.jss.2013.06.042

Cited by 25 publications

(18 citation statements)

References 37 publications

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“…This supports that the renoprotective effect of exendin‐4 may extend beyond glycaemic control to a direct effect on the kidney. Indeed, previous studies have demonstrated the protective effect of exendin‐4 against perfusion impairment induced by acute renal injuries in non‐diabetic animal models . Furthermore, the direct effect of exendin‐4 offers a plausible basis for the ability of exendin‐4 to alleviate oxidative stress, and endothelial dysfunction, and apoptosis in our study.…”

Section: Discussionsupporting

confidence: 58%

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

Hussien

Sorour

Elkerdasy

et al. 2018

Clin Exp Pharma Physio

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Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury, particularly in diabetic patients. Previous studies have shown renoprotective effects of glucagon-like peptide-1 (GLP-1) signalling; however, its role in CIN remains unexplored. This study investigates the prophylactic effect of exendin-4, a GLP-1R agonist, against CIN in a rat model mimicking both healthy and diabetic conditions. Animals were randomly divided into 7 groups: a control sham group (n = 8), and 2 identical sets of 3 disease groups, one received exendin-4 before exposure to contrast medium (CM), while the other served as untreated control. The 3 disease groups represented diabetes (n = 8), CIN (n = 8), or diabetes and CIN combined (n = 8). Untreated groups showed deteriorating renal function as indicated by significantly higher levels of serum creatinine and blood urea nitrogen, malondialdehyde, and endothelin-1 and caspase-3 expression compared to the sham control group. This was accompanied by a significant decrease in tissue reserves of reduced glutathione, superoxide dismutase, nitrate and endothelin nitric oxide synthase as well as deteriorating renal histology. The CM-induced changes in diabetic rats indicate impaired renal function, oxidative stress, vascular dysfunction, and apoptosis, and were significance higher in intensity compared to non-diabetic rats. Pretreatment with exendin-4 ameliorated all the aforementioned CM-induced nephropathic effects independent of the glycemic state. To our knowledge, this is the first study describing the prophylactic renoprotective effects of exendin-4 against CIN. With the current pharmaceutical use of exendin-4 as a hypoglycaemic agent, the GLP-1R agonist becomes an interesting candidate for human clinical trials on CIN prevention.

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Section: Discussionsupporting

confidence: 58%

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

Hussien

Sorour

Elkerdasy

et al. 2018

Clin Exp Pharma Physio

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“…The renal effects of DPP4i might be explained directly by its influence on GLP-1 and the legacy of better glycaemic control, or indirectly by glucose-independent mechanisms such as an alteration in blood pressure control and weight change [ 7 ]. GLP1 receptor activation protects against renal ischemic-reperfusion injury (IRI) through haeme-oxygenase 1 induction, an important model of experimental AKI [ 19 ]. In vitro and preclinical data also suggest that DPP4i reduces the activity of sodium-hydrogen exchanger 3 (NHE3) in proximal tubules, resulting in increased urinary sodium excretion and potentially lower blood pressure [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes

Chao

Wang

et al. 2017

Oncotarget

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ObjectivesDipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan.Materials and MethodsAll patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled. Propensity score-matched diabetic DPP4i users, who received DPP4i for at least 90 days, and nonusers were selected. The primary and secondary outcomes were incident AKI and dialysis-requiring AKI during follow-up. Cox proportional hazard analyses were performed to examine the effect of DPP4i on the risk of AKI.ResultsWe enrolled 923,936 diabetic patients; of these, 83,638 DPP4i users (75.7% sitagliptin, 14.6% vildagliptin, and 9.7% saxagliptin) were propensity score-matched to 83,638 non-users. After an average 3.6-year follow-up, 1.56% and 0.35% of DPP4i users and 2.53% and 0.56% of non-users developed incident AKI and dialysis-requiring AKI, respectively. DPP4i use was significantly associated with lower risk of incident AKI (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.53–0.61) and risk of dialysis-requiring AKI (HR 0.57, 95% CI 0.49–0.66). The risk reduction was consistent regardless of DPP4i type, the presence of chronic kidney disease, the previous acute kidney injury, and age.ConclusionsDPP4i use is associated with reduced risk of mild and severe forms of AKI among patients with incident DM. DPP4i may be an important class of anti-glycaemic agent with reno-protective effects.

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“…73 The preconditional activation of GLP-1R with exendin-4 also protected against ischemiareperfusion injury by increasing HO-1 expression. 74 The protective effect of GLP-1 is not likely to be restricted to the context of ischemia-reperfusion injury, and it apparently extends to toxic models of acute kidney injury. In mice subjected to cisplatin-induced renal injury, treatment with alogliptin significantly ameliorated injury by reducing apoptosis signaling.…”

Section: Incretin In Acute Kidney Injury Settingsmentioning

confidence: 99%

The potential for renoprotection with incretin-based drugs

Tanaka

Higashijima

Wada

et al. 2014

Kidney International

116

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Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions beyond glycemic control. Indeed, recent studies highlight the potential beneficial effects of incretin-based therapy in diabetic kidney disease (DKD). Experimental studies using various diabetic models suggest that incretins protect the vascular endothelium from injury by binding to GLP-1 receptors, thereby ameliorating oxidative stress and the local inflammatory response, which reduces albuminuria and inhibits glomerular sclerosis. In addition, there is some evidence that GLP-1 receptor agonists and DPP-4 inhibitors mediate sodium excretion and diuresis to lower blood pressure. The pleiotropic actions of DPP-4 inhibitors are ascribed primarily to their effects on GLP-1 signaling, but other substrates of DPP-4, such as brain natriuretic peptide and stromal-derived factor-1α, may have roles. In this review, we summarize recent studies of the roles of incretin-based therapy in ameliorating DKD and its complications.

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Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat

Cited by 25 publications

References 37 publications

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

Dipeptidyl peptidase 4 inhibitor use is associated with a lower risk of incident acute kidney injury in patients with diabetes

The potential for renoprotection with incretin-based drugs

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