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Published in: Diabetes Therapy 6/2018

Open Access 01-12-2018 | Original Research

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

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

Published in: Diabetes Therapy | Issue 6/2018

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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.
Literature
2.
go back to reference 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 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
3.
go back to reference Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis. 2014;63:S63–83.CrossRef Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis. 2014;63:S63–83.CrossRef
4.
go back to reference 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 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
5.
go back to reference 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 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
6.
go back to reference 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 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
7.
go back to reference 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 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
8.
go back to reference 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 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
9.
go back to reference Ryan D, Acosta A. GLP-1 receptor agonists: nonglycemic clinical effects in weight loss and beyond. Obesity (Silver Spring). 2015;23:1119–29.CrossRef Ryan D, Acosta A. GLP-1 receptor agonists: nonglycemic clinical effects in weight loss and beyond. Obesity (Silver Spring). 2015;23:1119–29.CrossRef
10.
go back to reference Skov J. Effects of GLP-1 in the kidney. Rev Endocr Metab Disord. 2014;15:197–207.CrossRef Skov J. Effects of GLP-1 in the kidney. Rev Endocr Metab Disord. 2014;15:197–207.CrossRef
11.
go back to reference 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, 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
12.
go back to reference 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 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
13.
go back to reference 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 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
14.
go back to reference 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. 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.
15.
go back to reference 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 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
16.
go back to reference Sedman T, Heinla K, Vasar E, Volke V. Liraglutide treatment may affect renin and aldosterone release. Horm Metab Res. 2017;49:5–9.PubMed Sedman T, Heinla K, Vasar E, Volke V. Liraglutide treatment may affect renin and aldosterone release. Horm Metab Res. 2017;49:5–9.PubMed
17.
go back to reference 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 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
18.
go back to reference 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. 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.
19.
go back to reference 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 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
20.
go back to reference 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 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
Metadata
Title
Glucagon-Like Peptide-1 Infusion Suppresses Aldosterone Levels in Healthy Normal-Weight Individuals: Double-Blind, Placebo-Controlled Crossover Study
Authors
Maja Baretić
Vesna Kušec
Ivana Pavlić-Renar
Publication date
01-12-2018
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 6/2018
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-018-0517-y

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