Glucagon-Like Peptide-1 Infusion Suppresses Aldosterone Levels in Healthy Normal-Weight Individuals: Double-Blind, Placebo-Controlled Crossover Study

Maja Baretić, Vesna Kušec, Ivana Pavlić-Renar, Maja Baretić, Vesna Kušec, Ivana Pavlić-Renar

Abstract

Introduction: 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).

Methods: 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.

Results: Three hours after GLP-1 infusion, aldosterone had decreased by a statistically significant amount (p < 0.008) compared to the baseline level.

Conclusion: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02130778.

Keywords: Aldosterone; Diabetes; GLP-1; Kidney; Nephropathy.

Figures

Fig. 1
Fig. 1
Study protocol
Fig. 2
Fig. 2
Suppression of aldosterone following infusion of GLP-1

References

    1. Rabkin R. Diabetic nephropathy. Clin Cornerstone. 2003;5:1–11. doi: 10.1016/S1098-3597(03)90014-7.
    1. Korner M., Stockli M., Waser B., Reubi J. C. GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting. Journal of Nuclear Medicine. 2007;48(5):736–743. doi: 10.2967/jnumed.106.038679.
    1. Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis. 2014;63:S63–S83. doi: 10.1053/j.ajkd.2013.10.047.
    1. 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;23:334–339. doi: 10.1038/ajh.2009.245.
    1. Anagnostis P., Athyros V. G., Adamidou F., Panagiotou A., Kita M., Karagiannis A., Mikhailidis D. P. Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diabetes, Obesity and Metabolism. 2011;13(4):302–312. doi: 10.1111/j.1463-1326.2010.01345.x.
    1. 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. doi: 10.1210/jc.2011-1508.
    1. 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;85:579–589. doi: 10.1038/ki.2013.427.
    1. 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;12:593–596.
    1. Ryan Donna, Acosta Andres. GLP-1 receptor agonists: Nonglycemic clinical effects in weight loss and beyond. Obesity. 2015;23(6):1119–1129. doi: 10.1002/oby.21107.
    1. Skov J. Effects of GLP-1 in the kidney. Rev Endocr Metab Disord. 2014;15:197–207. doi: 10.1007/s11154-014-9287-7.
    1. 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;89:3055–3061. doi: 10.1210/jc.2003-031403.
    1. 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;73:142–150. doi: 10.1159/000094334.
    1. 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–E671. doi: 10.1210/jc.2012-3855.
    1. 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.
    1. 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;61:2967–2979. doi: 10.2337/db11-1824.
    1. Sedman T, Heinla K, Vasar E, Volke V. Liraglutide treatment may affect renin and aldosterone release. Horm Metab Res. 2017;49:5–9.
    1. 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;377:839–848. doi: 10.1056/NEJMoa1616011.
    1. 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.
    1. 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;140:5356–5363. doi: 10.1210/endo.140.11.7143.
    1. 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;93:2263–2266. doi: 10.1172/JCI117225.

Source: PubMed

3
Suscribir