To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.7111430.
Glucagon-like peptide-1 (GLP-1) has many effects on the human body, but its glucose-lowering effect through its stimulation of insulin secretion is the most significant. GLP-1 also acts on renal function and hemodynamics. The antihypertensive and renoprotective effects of GLP-1 receptor agonists are partly explained by their vasoactive effect and increased natriuresis, but their positive influences on blood pressure and the development and progression of kidney disease are attributed to many effects beyond glycemic control. The aim of this study was to determine how the native gut hormone GLP-1 influences the renin–angiotensin–aldosterone system (RAAS).
Fourteen healthy participants (6 males and 8 females) were included in a double-blind, placebo-controlled crossover study. After overnight fasting and oral sodium loading, participants were randomly assigned to receive either placebo (500 ml of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min dissolved in 500 ml of 0.9% saline) over a 3-h period. After 3 and 6 h, the following parameters were measured: glucose, insulin, plasma renin activity, aldosterone, GLP-1, and antidiuretic hormone. After 7 days, the protocol was repeated, except that those who had previously received placebo now received GLP-1 infusion, and those who had previously received GLP-1 now received placebo.
Three hours after GLP-1 infusion, aldosterone had decreased by a statistically significant amount (p < 0.008) compared to the baseline level.
The present study showed that native GLP-1 can decrease aldosterone secretion in a group of healthy individuals, supporting the idea of beneficial outcomes of GLP-1-activating agents on blood pressure and the RAAS.
ClinicalTrials.gov Identifier: NCT02130778.
Rabkin R. Diabetic nephropathy. Clin Cornerstone. 2003;5:1–11. CrossRef
Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007;48:736–43. CrossRef
Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis. 2014;63:S63–83. CrossRef
Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010;23:334–9. CrossRef
Anagnostis P, Athyros VG, Adamidou F, Panagiotou A, Kita M, Karagiannis A, Mikhailidis DP. Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diabetes Obes Metab. 2011;13:302–12. CrossRef
Chaudhuri A, Ghanim H, Vora M, Sia CL, Korzeniewski K, Dhindsa S, et al. Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab. 2012;97:198–207. CrossRef
Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M, et al. The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney Int. 2014;85:579–89. CrossRef
Malendowicz LK, Neri G, Nussdorfer GG, Nowak KW, Zyterska A, Ziolkowska A. Prolonged exendin-4 administration stimulates pituitary-adrenocortical axis of normal and streptozotocin-induced diabetic rats. Int J Mol Med. 2003;12:593–6. PubMed
Ryan D, Acosta A. GLP-1 receptor agonists: nonglycemic clinical effects in weight loss and beyond. Obesity (Silver Spring). 2015;23:1119–29. CrossRef
Skov J. Effects of GLP-1 in the kidney. Rev Endocr Metab Disord. 2014;15:197–207. CrossRef
Gutzwiller JP, Tschopp S, Bock A, Zehnder CE, Huber AR, Kreyenbuehl M, et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004;89:3055–61. CrossRef
Gutzwiller JP, Hruz P, Huber AR, Hamel C, Zehnder C, Drewe J, et al. Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans. Digestion. 2006;73:142–50. CrossRef
Skov J, Dejgaard A, Frøkiær J, Holst JJ, Jonassen T, Rittig S, et al. Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J Clin Endocrinol Metab. 2013;98:E664–71. CrossRef
Jelaković B, Kaić-Rak A, Milicić D, Premuzić V, Skupnjak B, Reiner Z. Less salt—more health. Croatian Action on Salt and Health (CRASH). Lijec Vjesn. 2009;131:87–92.
Mima A, Hiraoka-Yamomoto J, Li Q, Kitada M, Li C, Geraldes P, et al. Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCbeta activation in diabetes. Diabetes. 2012;61:2967–79. CrossRef
Sedman T, Heinla K, Vasar E, Volke V. Liraglutide treatment may affect renin and aldosterone release. Horm Metab Res. 2017;49:5–9. PubMed
Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377:839–48. CrossRef
Persson F, Lindhardt M, Rossing P, Parving HH. Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes: a systematic review. J Renin Angiotensin Aldosterone Syst. 2016;3:17.
Hansen L, Deacon CF, Orskov C, Holst JJ. Glucagon-like peptide-1-(7-36) amide is transformed to glucagon-like peptide-1-(9-36) amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology. 1999;140:5356–63. CrossRef
D’Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Investig. 1994;93:2263–6. CrossRef
- Glucagon-Like Peptide-1 Infusion Suppresses Aldosterone Levels in Healthy Normal-Weight Individuals: Double-Blind, Placebo-Controlled Crossover Study
- Springer Healthcare
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II