Abstract
Acute kidney injury (AKI) is common in patients with sepsis and causes renal ischemia. Glucagon-like peptide-1 (GLP-1) protects the vascular system and the kidney, and GLP-1 receptor (GLP-1R) is expressed in the kidney. Renal GLP-1R activity is decreased in chronic kidney disease (CKD), but is increased by the inflammatory response; however, the effect of AKI on GLP-1R expression is unknown. We investigated the role of GLP-1 by assessing GLP-1R expression in the renal cortex in animals with AKI-related sepsis, CKD, and CKD-with-sepsis. We generated a model of CKD by 5/6 nephrectomy, and sepsis induced by cecal perforation, in male Sprague–Dawley rats. We compared renal GLP-1R expression at 3, 6, 12, 24, and 72 h after cecal perforation, and in CKD and CKD-with-sepsis. We performed blood and urine tests, western blotting (WB), and immunohistochemistry (IHC) to assay GLP-1R expression in renal tubules. The CKD-with-sepsis group showed the lowest kidney function, urine volume, and serum glucose and albumin levels. GLP-1R expression in renal tubules was decreased at 3 h, increased at 24 h, and decreased at 72 h after sepsis induction. GLP-1R expression was decreased at 8 weeks after CKD and was lowest in the CKD-with-sepsis group. The WB results were verified against those obtained by IHC. GLP-1R expression in renal tubules is increased in early sepsis, which may explain the protective effect of endogenous GLP-1 against sepsis-related inflammation.
Highlights
Sepsis is an important cause of acute kidney injury (AKI), which has a mortality rate approaching 70% [1]
GLP-1 receptor (GLP-1R) expression in renal tubules was increased in early sepsis and later decreased by kidney injury, but was decreased in the chronic kidney disease (CKD) and CKD-with-sepsis groups
Renal GLP-1R expression was shown to be increased by DPP-4 in experimental animals [25], as we reported in an earlier study [15]
Summary
Sepsis is an important cause of acute kidney injury (AKI), which has a mortality rate approaching 70% [1]. Systemic and intra-renal vasoconstriction causes renal tubular ischemia in sepsis [2], and adequate fluid supply is needed to improve renal perfusion [3]. Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced in the small intestine, which enhances insulin secretion after blood glucose elevation. GLP-1 analogues are used clinically for glycemic control [6]. GLP-1 protects vascular endothelial and myocardial cells [7], and exerts a renoprotective effect [8,9]. GLP-1 receptor (GLP-1R) is expressed in the pancreas, central nervous system, heart, and intestine and regulates insulin secretion and vasodilation [10,11]. GLP-1R is expInrte.sJ.sMedol.iSncit. h20e19g,l2o0m, xeFrOuRliPaEEnRdRpErVoIExWimal tubules of the kidney [12]
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