GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment

Krass, Maarja; Volke, Annika; Rünkorg, Kertu; Wegener, Gregers; Lund, Sten; Abildgaard, Anders; Vasar, Eero; Volke, Vallo

doi:10.1017/neu.2014.36

Cited by 24 publications

(24 citation statements)

References 26 publications

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“…It is well established that psychological stress can accelerate cardiovascular disorder initiation and progression via either depression or activation of the hypothalamic–pituitary–adrenal feedback mechanisms . Previous studies reported that GLP‐1R agonists have a sustained stimulatory effect on neurohormone (ie, corticosterone) secretion in animals . We have shown that chronic stress markedly suppressed the plasma corticosterone level; this effect was restored by the treatment with anagliptin and exenatide.…”

Section: Discussionmentioning

confidence: 55%

“…6 Previous studies reported that GLP-1R agonists have a sustained stimulatory effect on neurohormone (ie, corticosterone) secretion in animals. 47,48 We have shown that chronic stress markedly suppressed the plasma corticosterone level; this effect was restored by the treatment with anagliptin and exenatide. Recently, we have demonstrated that chronic stress also increased plasma adrenaline and noradrenaline levels, and these changes were reversed by both drugs.…”

Section: Discussionmentioning

confidence: 96%

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Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

Piao

Zhao

Zhu

et al. 2017

JAHA

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BackgroundExposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase‐4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon‐like peptide‐1 (GLP‐1) metabolism, we investigated the role of DPP4/GLP‐1 axis in vascular senescence and ischemia‐induced neovascularization in mice under chronic stress, with a special focus on adiponectin ‐mediated peroxisome proliferator activated receptor‐γ/its co‐activator 1α (PGC‐1α) activation.Methods and ResultsSeven‐week‐old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood‐flow ratio throughout the follow‐up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP‐1 and adiponectin in plasma and phospho‐AMP‐activated protein kinase α (p‐AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor‐γ, PGC‐1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31+/c‐Kit+ progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP‐1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion.ConclusionsThese results indicate that the DPP4/GLP‐1‐adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 96%

Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

Piao

Zhao

Zhu

et al. 2017

JAHA

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“…; Krass et al . ). Glucocorticoids are known to increase intestinal sodium and water absorption from small and large intestine as a result of their effect on Na + /K + ATPase, NHE3 and SGLT1 activity.…”

Section: Discussionmentioning

confidence: 97%

Role of enteroendocrine L‐cells in arginine vasopressin‐mediated inhibition of colonic anion secretion

Pais

Rievaj

Meek

et al. 2016

The Journal of Physiology

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r By means of Ussing chambers, we show that AVP reduced colonic anion secretion, although this was blocked by a specific neuropeptide Y receptor Y1 receptor antagonist, suggesting that L-cell-released PYY acts locally on the epithelium to modulate fluid balance.r In human serum samples, PYY concentrations were higher in samples with raised osmolality and copeptin (surrogate marker for AVP).r These findings describe, for the first time, the role of L-cells in AVP regulated intestinal fluid secretion, potentially linking together hormonal control of blood volume and blood glucose levels, and thus adding to our understanding of the complex pathways involved in the gut hormonal response to different stimuli.Abstract Arginine vasopressin (AVP) regulates fluid balance and blood pressure via AVP receptor (AVPR)2 in the kidney and AVP receptor 1A in vascular smooth muscle. Its role in intestinal function has received less attention. We hypothesized that enteroendocrine L-cells producing glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) may be a target of AVP and contribute to the control of fluid balance. Avpr1b expression was assessed by quantitative RT-PCR on flourescence-activated cell sorting-isolated L-and control cells and was enriched in colonic L-cells. AVP stimulated GLP-1 and PYY release from primary cultured murine and human colonic cells and was associated with elevated calcium and cAMP concentrations in L-cells as measured in cultures from GLU-Cre/ROSA26-GCaMP3 and GLU-Epac2camps mice. An antagonist of AVPR1B reduced AVP-triggered hormone secretion from murine and human cells. In Ussing chambers, basolaterally applied AVP reduced colonic anion secretion and this effect was blocked by a specific neuropeptide Y receptor Y1 (NPY1R) antagonist. In human serum, PYY concentrations were higher in samples with raised osmolality or copeptin (a surrogate marker for AVP). In conclusion, we propose that AVP activates L-cell AVPR1B, causing GLP-1 and PYY secretion. PYY in turn reduces colonic anion secretion via epithelial NPY1R. Our data suggest L-cells are active players in the hypothalamic control of intestinal fluid homeostasis, providing a potential link between the regulation of blood volume/pressure/osmolality and blood glucose.

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“…It has been demonstrated that peripheral administration of GLP-1 agonists significantly increases circulating glucocorticoid and aldosterone levels in both rodents and humans [12,13]. Our group has previously demonstrated that acute administration of a GLP-1 receptor agonist induces a significant increase in glucocorticoid levels in mice [14,15]. Furthermore, tolerance did not develop towards corticosterone release after chronic treatment with the GLP-1 receptor agonists exenatide or liraglutide [14].…”

Section: Introductionmentioning

confidence: 90%

Liraglutide Treatment May Affect Renin and Aldosterone Release

et al. 2016

Self Cite

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Nowadays, GLP-1 receptor agonists are widely used as effective and safe antidiabetic medications. In addition to glucose-dependent insulin secretion, their effects reach beyond glucose control. Previously, it has been shown that acute administration of GLP-1 receptor agonists increases circulating glucocorticoid and mineralocorticoid levels in both humans and rodents. So far, no studies have reported the effects of chronic administration of GLP-1 receptor agonists on the hypothalamic-pituitary-adrenal axis in humans. The aim of the current study was to examine the effects of acute and chronic treatment with the GLP-1 receptor agonist liraglutide on adrenal function in humans. Ten healthy volunteers were recruited into a single group open-label clinical trial. Each participant was tested for baseline levels, and after acute and chronic treatment with 0.6 mg liraglutide daily. A graded glucose infusion test was performed 3 times. We found that aldosterone tended to be suppressed (albeit not statistically different) after acute administration of liraglutide, and increased after chronic dosing; the difference was statistically significant when compared between acute and chronic dosing. Changes in aldosterone levels followed the changes in renin concentrations and the aldosterone-to-renin ratio remained stable. No statistically significant differences were observed in ACTH or cortisol levels. In conclusion, we have shown that a low dose of GLP-1 receptor agonist may interfere with renin and aldosterone release. Further studies in a larger patient sample and with higher doses of GLP-1 receptor agonists are warranted to corroborate this finding. The study protocol was registered at clinical.trials.gov (NCT02089256) and EU Clinical Trial Register (2014-000238-43).

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GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment

Abstract: The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

Cited by 24 publications

References 26 publications

Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

Role of enteroendocrine L‐cells in arginine vasopressin‐mediated inhibition of colonic anion secretion

Liraglutide Treatment May Affect Renin and Aldosterone Release

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