A GLP-1 Receptor Agonist Inhibits Aldosterone Release in Healthy Volunteers

2021 ◽  
Vol 53 (06) ◽  
pp. 402-407
Author(s):  
Tuuli Sedman ◽  
Vallo Volke ◽  
Keiu Heinla ◽  
Eero Vasar
Keyword(s):  
Healthy Volunteers ◽  
Ambulatory Setting ◽  
Controlled Study ◽  
Acute Administration ◽  
Open Label ◽  
Glucose Levels ◽  
Adrenal Axis ◽  
Blood Glucose Levels ◽  
Glucagon Like Peptide 1 ◽  
Pituitary Adrenal Axis

AbstractGlucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

scholarly journals Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system

2010 ◽  
Vol 298 (5) ◽  
pp. E1088-E1096 ◽  
Author(s):  
Diego Pérez-Tilve ◽  
Lucas González-Matías ◽  
Benedikt A. Aulinger ◽  
Mayte Alvarez-Crespo ◽  
Manuel Gil-Lozano ◽  
...  
Keyword(s):  
Nervous System ◽  
Blood Glucose ◽  
Sympathetic Nervous System ◽  
Mammalian Species ◽  
Chronic Administration ◽  
Acute Administration ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sympathetic Nervous ◽  
High Doses

Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.

scholarly journals Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes

2019 ◽  
Vol 116 (5) ◽  
pp. 916-930 ◽  
Author(s):  
Valerie D Heuvelman ◽  
Daniël H Van Raalte ◽  
Mark M Smits
Keyword(s):  
Cardiovascular Disease ◽  
Blood Glucose ◽  
Cardiovascular Effects ◽  
Lifestyle Changes ◽  
Mechanistic Studies ◽  
Receptor Agonists ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Type 2 diabetes mellitus (T2DM) is currently one of the most prevalent diseases, with as many as 415 million patients worldwide. T2DM is characterized by elevated blood glucose levels and is often accompanied by several comorbidities, such as cardiovascular disease. Treatment of T2DM is focused on reducing glucose levels by either lifestyle changes or medical treatment. One treatment option for T2DM is based on the gut-derived hormone glucagon-like peptide 1 (GLP-1). GLP-1 reduces blood glucose levels by stimulating insulin secretion, however, it is rapidly degraded, and thereby losing its glycaemic effect. GLP-1 receptor agonists (GLP-1RAs) are immune to degradation, prolonging the glycaemic effect. Lately, GLP-1RAs have spiked the interest of researchers and clinicians due to their beneficial effects on cardiovascular disease. Preclinical and clinical data have demonstrated that GLP-1 receptors are abundantly present in the heart and that stimulation of these receptors by GLP-1 has several effects. In this review, we will discuss the effects of GLP-1RA on heart rate, blood pressure, microvascular function, lipids, and inflammation, as measured in human mechanistic studies, and suggest how these effects may translate into the improved cardiovascular outcomes as demonstrated in several trials.

Sign in / Sign up

Export Citation Format

Share Document