Abstract
BackgroundGlucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP4) inhibitors are a newer class of antidiabetics named as incretin-based therapy. In addition to the homeostatic control of glucose, the incretin-based therapy has shown beneficial effects on the cardiovascular system in preclinical and clinical studies. However, there is limited information on their renal effects. To this end, we assessed the acute hemodynamic and renal effects of a GLP-1 analog, Liraglutide, and a DPP4 inhibitor, MK-0626.MethodsExperiments were performed in anesthetized male Sprague–Dawley rats. Three ascending doses of Liraglutide (3, 9, and 27 nmol/kg/h) or MK-0626 (1 mg/kg) with or without GLP-1 peptide (2.4, 4.8, or 9.6 pmol/kg/min) were administered. Blood pressure (BP) and heart rate (HR) were recorded from an indwelling catheter. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by inulin and para-aminohippurate clearance, respectively. Renal excretory function was assessed in metabolic studies.ResultsBoth Liraglutide and MK-0626 plus GLP-1 evoked significant diuretic and natriuretic responses and increased GFR. MK-0626 alone increased RBF. Liraglutide at 27 nmol//kg/h and MK-0626 plus GLP-1 at 9.6 pmol/kg/min also increased HR, whereas BP was not affected.ConclusionThe results of the present study demonstrated that a GLP-1 analog and a DPP4 inhibitor may have beneficial effects on renal sodium and water handling. Additionally, the DPP4 inhibitor, MK-0626, favorably affects renal hemodynamics by increasing RBF. However, exceedingly high levels of GLP-1 receptor agonists may adversely affect the cardiovascular system in acute setting, as demonstrated by an acute increase in HR.
Highlights
Incretins, including glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide, known as glucosedependent insulinotropic polypeptide (GIP) are a class of gastrointestinal hormones released from the small intestine in response to the presence of food
The intravenous infusion of Liraglutide (9 and 27 nmol/kg/h) significantly increased heart rate (HR); blood pressure (BP) remained unchanged at all doses of Liraglutide (Table 2)
At the end of the Liraglutide infusion, the plasma glucose level was slightly higher than at baseline (Table 3); we speculate this is attributable to the substantial diuresis/natriuresis induced by Liraglutide, which led to extracellular volume contraction and hemoconcentration
Summary
Incretins, including glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide, known as glucosedependent insulinotropic polypeptide (GIP) are a class of gastrointestinal hormones released from the small intestine in response to the presence of food. Sitagliptin decreased systolic BP, increased renal blood flow (RBF) [5], and improved endothelial function through reducing oxidative stress in adult SHRs [6]. Recombinant GLP-1 infusion improved cardiac function in patients with chronic heart failure or with acute myocardial infarction and severe systolic dysfunction [15,16,17,18]. Glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP4) inhibitors are a newer class of antidiabetics named as incretin-based therapy. In addition to the homeostatic control of glucose, the incretin-based therapy has shown beneficial effects on the cardiovascular system in preclinical and clinical studies. There is limited information on their renal effects To this end, we assessed the acute hemodynamic and renal effects of a GLP-1 analog, Liraglutide, and a DPP4 inhibitor, MK-0626
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