Central Apelin Controls Glucose Homeostasis<i>via</i>a Nitric Oxide-Dependent Pathway in Mice

Duparc, Thibaut; Colom, André; Cani, Patrice D.; Massaly, Nicolas; Rastrelli, Sophie; Drougard, Anne; Gonidec, Sophie Le; Moulédous, Lionel; Francés, Bernard; Leclercq, Isabelle; Llorens-Cortes, Catherine; Pospisilik, J. Andrew; Delzenne, Nathalie M.; Valet, Philippe; Castan-Laurell, Isabelle; Knauf, Claude

doi:10.1089/ars.2010.3454

Cited by 66 publications

(93 citation statements)

References 48 publications

(61 reference statements)

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“…Furthermore, there is a greater expression in white adipose tissue compared with the subcutaneous adipose tissue in accordance with the data of OLEFT rats [81,82]. Several research groups have found gender differences in serum vaspin.…”

Section: Vaspinsupporting

confidence: 87%

“…Visceral adipose tissue-derived serpin (vaspin), is a member of serine protease inhibitor (SERPIN) family, first identified as a new gene, OL-64, expressed in visceral adipose tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of abdominal obesity and type 2 diabetes [80,81]. Vaspin expression was also found in hypothalamus, stomach and pancreatic islets [82] but is not expressed in the subcutaneous tissue, brown adipose tissue and other not fat tissues.…”

Section: Vaspinmentioning

confidence: 99%

“…In humans, the vaspin is expressed in adipose tissue, stomach, liver and pancreas to a greater extent in overweight and obese compared to lean subjects 81 . Furthermore, there is a greater expression in white adipose tissue compared with the subcutaneous adipose tissue in accordance with the data of OLEFT rats [81,82].…”

Section: Vaspinmentioning

confidence: 99%

“…Vaspin was associated to inhibition of TNF-α induced expression of intercellular adhesion molecule (ICAM) by preventing ROS generation and subsequent activation of NF-kB [90]. Fat mass expansion was associated with increased vaspin expression and its circulating concentration [81,83,91]. In obese subjects, it was shown that serum vaspin decreased following modest weight loss accompanied by improved parameters relevant to insulin resistance [92].…”

Section: Vaspinmentioning

confidence: 99%

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Adipokines and their Involvement as a Target of New Drugs

Raimo¹

2015

J Pharmacovigil

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Globesity is referred to a global epidemic of obesity, affecting millions of individuals. Molecules released by the enlarged adipose tissue, most of which are pro-inflammatory, have been named adipokines. The present review deals with function, molecular targets and the potential clinical relevance of adipokines. Currently, more than 600 adipokines have been identified, many of them, including leptin, visfatin, resistin as well as Retinol Binding Protein4 may serve as informative markers for metabolic and cardiovascular diseases and play important roles in glucose homeostasis, insulin sensitivity as well as metabolic regulation of energy expenditure. Adiponectin on the contrary exerts anti-inflammatory and insulin sensitizing activity. Adiponectin has additional anti-atherogenic effects and low adiponectin serum concentrations are associated with in creased risk for cardiovascular diseases. The understanding of the role of adipokines has provided a wealth of information that has opened great opportunities for new therapeutic advances. Adiponectin may be the most prominent example for the potential use of an adipokine in the treatment of obesity and obesity-associated metabolic diseases. In many studies, administration of recombinant adiponectin results in improved insulin sensitivity, increased insulin secretion and beneficial effects on body weight and hyperglycemia. Up-regulation of adiponectin/adiponectin receptors or enhancing adiponectin receptor function may be an interesting therapeutic strategy for obesity-linked insulin resistance. Moreover, the therapeutic use of combined amylin/leptin agonism (with pramlintide and metreleptin) demonstrated a significant weight-lowering effect in obese subjects. Therefore, adipokines may be clinically relevant either as therapeutic tools or as target in the treatment of obesity related diseases. Journal of PharmacovigilanceJou rn a l o f P harma c o v ig il a nc e

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Section: Vaspinsupporting

confidence: 87%

Section: Vaspinmentioning

confidence: 99%

Section: Vaspinmentioning

confidence: 99%

Section: Vaspinmentioning

confidence: 99%

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Adipokines and their Involvement as a Target of New Drugs

Raimo¹

2015

J Pharmacovigil

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“…In the isolated rat aorta, apelin stimulates the transport of L-arginine and enhances the activity of eNOS to stimulate the production of nitric oxide (Jia et al 2007), while post-infarct treatment of rats with (Pyr 1 )apelin-13 significantly increases serum nitric oxide levels (Azizi et al 2013). Apelin has also been implicated in signalling via NOS in the aortic ring of diabetic mice and in the control of glucose metabolism in mice, as validated by studies carried out with a NOS inhibitor and eNOS knockout (KO) mice (Zhong et al 2007, Duparc et al 2011. However, the cardioprotective role of apelin in mice does not appear to be mediated via eNOS activity ).…”

Section: ) Similar Findings Have Been Observed In Mice Where Apmentioning

confidence: 99%

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

O’Carroll

Lolait

Harris

et al. 2013

Journal of Endocrinology

288

216

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The apelin receptor (APJ; gene symbol APLNR) is a member of the G protein-coupled receptor gene family. Neural gene expression patterns of APJ, and its cognate ligand apelin, in the brain implicate the apelinergic system in the regulation of a number of physiological processes. APJ and apelin are highly expressed in the hypothalamo-neurohypophysial system, which regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis, which controls the neuroendocrine response to stress, and in the forebrain and lower brainstem regions, which are involved in cardiovascular function. Recently, apelin, synthesised and secreted by adipocytes, has been described as a beneficial adipokine related to obesity, and there is growing awareness of a potential role for apelin and APJ in glucose and energy metabolism. In this review we provide a comprehensive overview of the structure, expression pattern and regulation of apelin and its receptor, as well as the main second messengers and signalling proteins activated by apelin. We also highlight the physiological and pathological roles that support this system as a novel therapeutic target for pharmacological intervention in treating conditions related to altered water balance, stress-induced disorders such as anxiety and depression, and cardiovascular and metabolic disorders.

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Apelinergic System Structure and Function

Shin

Kenward

Rainey

2017

Comprehensive Physiology

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Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein-coupled receptor named the apelin receptor (AR/APJ/APLNR). Ligand-AR interactions have been implicated in regulation of the adipoinsular axis, cardiovascular system, and central nervous system alongside pathological processes. Each ligand may be processed into a variety of bioactive isoforms endogenously, with apelin ranging from 13 to 55 amino acids and apela from 11 to 32, typically being cleaved C-terminal to dibasic proprotein convertase cleavage sites. The C-terminal region of the respective precursor protein is retained and is responsible for receptor binding and subsequent activation. Interestingly, both apelin and apela exhibit isoform-dependent variability in potency and efficacy under various physiological and pathological conditions, but most studies focus on a single isoform. Biophysical behavior and structural properties of apelin and apela isoforms show strong correlations with functional studies, with key motifs now well determined for apelin. Unlike its ligands, the AR has been relatively difficult to characterize by biophysical techniques, with most characterization to date being focused on effects of mutagenesis. This situation may improve following a recently reported AR crystal structure, but there are still barriers to overcome in terms of comprehensive biophysical study. In this review, we summarize the three components of the apelinergic system in terms of structure-function correlation, with a particular focus on isoform-dependent properties, underlining the potential for regulation of the system through multiple endogenous ligands and isoforms, isoform-dependent pharmacological properties, and biological membrane-mediated receptor interaction. © 2018 American Physiological Society. Compr Physiol 8:407-450, 2018.

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Central Apelin Controls Glucose Homeostasisviaa Nitric Oxide-Dependent Pathway in Mice

Abstract: These data provide compelling evidence that central apelin participates in the regulation of glucose homeostasis and suggest a novel pathophysiological mechanism involved in the transition from normal to diabetic state.

Cited by 66 publications

References 48 publications

Adipokines and their Involvement as a Target of New Drugs

Adipokines and their Involvement as a Target of New Drugs

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

Apelinergic System Structure and Function

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