Abstract
Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone increasing postprandial insulin release. GLP‐1 also induces diuresis and natriuresis in humans and rodents. The GLP‐1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP‐1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP‐1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP‐1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP‐1. We hypothesized that GLP‐1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP‐1 receptor were used to localize GLP‐1 receptors in the kidney. Sevoflurane‐anesthetized normotensive Sprague–Dawley rats and SHR received a 20 min intrarenal infusion of GLP‐1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP‐1 was assessed in isolated interlobar arteries from normo‐ and hypertensive rats. We found no expression of GLP‐1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP‐1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP‐1 in SHR are caused either by extrarenal GLP‐1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP‐1 receptor.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease which has been declared a global epidemic and the number of patients is increasing
In spontaneously hypertensive rats (SHR), there were no Glucagon-like peptide-1 (GLP-1) receptor immunoreactive cells in the renal tissue (Fig. 1D), showing that there are no renal GLP-1 receptors expressed in SHR
There was GLP-1 receptor-positive staining in the renal vasculature from SD rats (Fig. 2C), whereas there was very low or no GLP-1 receptor-positive staining in the vasculature from SHR (Fig. 2D)
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease which has been declared a global epidemic and the number of patients is increasing. T2DM is often associated with hypertension and both are leading causes in the development of renal failure (Emdin et al 2015). Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L-cells in the small intestine. GLP-1 is secreted as the active intact GLP-1 (7–36) amide, but is rapidly degraded to GLP-1 (9–36) amide by the ubiquitously expressed enzyme dipeptidyl peptidase-4 (DPP-4). This results in a very short in vivo half-life of a 2017 The Authors.
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