Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9BY76 (adipokine)
 3,147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apelin is the endogenous ligand of the G-protein coupled apj receptor. Apelin is expressed in the brain, the hypothalamus and the stomach and was recently shown also to be an adipokine secreted from the adipocytes. Although apelin has been suggested to be involved in the regulation of food intake, it is not known whether the peptide affects islet function and glucose homeostasis. We show here that the apj receptor is expressed in pancreatic islets and that intravenous administration of full-length apelin-36 (2 nmol/kg) inhibits the rapid insulin response to intravenous glucose (1 g/kg) by 35% in C57BL/6J mice. Thus, the acute (1-5 min) insulin response to intravenous glucose was 682+/-23 pmol/l after glucose alone (n=17) and 445+/-58 pmol/l after glucose plus apelin-36 (n=18; P=0.017). This was associated with impaired glucose elimination (the 5-20 min glucose elimination was 2.9+/-0.1%/min after glucose alone versus 2.3+/-0.2%/min after glucose plus apelin-36, P=0.008). Apelin (2 nmol/kg) also inhibited the insulin response to intravenous glucose in obese insulin resistant high-fat fed C57BL/6J mice (P=0.041). After 60 min incubation of isolated islets from normal mice, insulin secretion in the presence of 16.7 mmol/l glucose was inhibited by apelin-36 at 1 mumol/l, whereas apelin-36 did not significantly affect insulin secretion at 2.8 or 8.3 mmol/l glucose or after stimulation of insulin secretion by KCl. Islet glucose oxidation at 16.7 mmol/l was not affected by apelin-36. We conclude that the apj receptor is expressed in pancreatic islets and that apelin-36 inhibits glucose-stimulated insulin secretion both in vivo and in vitro. This may suggest that the islet beta-cells are targets for apelin-36.
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PMID:The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice. 1597 Mar 38

Apelin is a recently discovered vasoactive peptide that has been demonstrated to be the endogenous ligand of the APJ receptor. It was named 'apelin' after APJ endogenous ligand. This G protein-coupled receptor (GPCR), originally identified by O'Dowd et al. in 1993, has a close identity with the angiotensin II type 1 (AT1) receptor, but does not bind angiotensin-II. Although apelin and APJ have been found to be ubiquitously expressed in peripheral tissues, particularly the heart and lungs, as well as various regions of the central nervous system, the physiologic actions of apelin remain largely unknown. Nevertheless, some cardiovascular functions of the apelin/APJ system have been described, such as endothelium-dependent vasodilatation, vasoconstriction by direct action on the smooth muscle and positive inotropism. Other reported physiologic actions of apelin include: (1) its role as endocrine adipokine; (2) contribution to fluid homeostasis and thirst regulation; (3) participation as coreceptor in the process of human immunodeficiency virus type 1 infection; and (4) regulation of immune response. The involvement of apelin/APJ in the pathophysiology of heart failure (HF) and its potential as a therapeutic target in this syndrome have also been proposed. In the course of HF progression, plasma levels of apelin are significantly increased in the early stages, decreasing progressively towards normal in the advanced stages of the disease. Given the increasing number of studies focusing on the apelin/APJ system, the goal of this paper was to make an up-to-date review of existing information on apelin and APJ, with particular focus on their cardiovascular actions and potential use as a therapeutic target in HF.
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PMID:Apelin: a novel neurohumoral modulator of the cardiovascular system. Pathophysiologic importance and potential use as a therapeutic target. 1639 42

The apelin receptor was initially classed as an orphan G-protein-coupled receptor, and little was known about its physiological functions until apelin, the endogenous ligand, was identified. Similarities between the structure and anatomical distribution of apelin and its receptor and that of angiotensin II and the angiotensin AT1 receptor provide clues about the physiological functions of this novel signal-transduction system. Now, roles have been established for the apelin system in lowering blood pressure, as a potent cardiac inotrope, in modulating pituitary hormone release and food and water intake, in stress activation, and as a novel adipokine that is excreted from fat cells and regulates insulin. Given its broad array of physiological roles, apelin has attracted much interest as a target for novel therapeutic research and drug design.
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PMID:Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity. 1653 Aug 55

We have recently identified apelin as a novel adipokine up-regulated by insulin and obesity. Since obesity and insulin resistance are associated with chronically elevated levels of both insulin and TNFalpha, the present study was performed to investigate a putative regulation of apelin expression in adipocytes by TNFalpha. Herein, we report a tight correlation between apelin and TNFalpha expression in adipose tissue of lean and obese humans. Apelin regulation by TNFalpha was further studied in cultured explants of human adipose tissue. The endogenous expression of TNFalpha in adipocytes isolated from the explants was accompanied by a 6-9 h subsequent increase of apelin expression in adipocytes. This increase was reversed by inhibiting TNFalpha expression with 100 microM isobutylmethylxanthine. In different mouse models of obesity, expression of both TNFalpha and apelin was also significantly increased in adipocytes of obese mice. Furthermore, short-term exposure to an i.p. injection of TNFalpha in C57Bl6/J mice induced an increase of apelin expression in adipose tissue as well as apelin plasma levels. Finally, a direct positive effect of TNFalpha has been shown in differentiated 3T3F442A adipocytes on apelin expression and secretion. The signaling pathways of TNFalpha for the induction of apelin were dependent of PI3-kinase, c-Jun NH2-terminal kinase (JNK), and MAPK but not PKC activation. All together, these findings suggest that apelin might be a candidate to better understand potential links between obesity and associated disorders such as inflammation and insulin resistance.
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PMID:TNFalpha up-regulates apelin expression in human and mouse adipose tissue. 1672 81

Gravidas with obesity and diabetes ("diabesity") may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr(db/+) diabese mouse to examine the magnitude of these transmission modes, focusing on adipose tissue (AT). We compared the following six groups: wild-type (+/+) offspring from +/+ or db/+ dams (different early life environment) and db/+ offspring from db/+ dams, fed a standard or high-fat diet. Weight gain (0-8 wk) was higher in +/+ offspring from db/+ vs. +/+ mothers, and even higher in db/+ vs. +/+ offspring from db/+ mothers. In addition, we observed a stepwise increase in AT and adipocyte size in +/+ from +/+ mice, +/+ from db/+ mice, and db/+ mice at 8 wk. Differences in weight and adiposity between +/+ offspring from db/+ vs. +/+ dams were more pronounced in males than in females. Leptin and apelin mRNA levels in white and brown AT were higher in +/+ offspring from db/+ vs. +/+ dams; however, leptin, apelin, and tumor necrosis factor-alpha expression were boosted more robustly in db/+ offspring. The high-fat diet amplified AT differences between db/+ vs. +/+ offspring from db/+ dams, but not between +/+ offspring from db/+ vs. +/+ dams. Moreover, db/+ but not +/+ offspring from db/+ mothers were insulin-resistant and hyperinsulinemic after a glucose challenge. In conclusion, the genetic transmission of the diabesity phenotype clearly prevailed, but the early-life diabesity environment had discernible effects on postnatal weight gain as well as on adipocyte size and adipokine expression at a postpubertal age.
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PMID:Adipose tissue in offspring of Lepr(db/+) mice: early-life environment vs. genotype. 1695 32

Recently, apelin was characterised as a novel adipose-expressed factor which is upregulated in rodent and human obesity and influences cardiovascular function, as well as insulin secretion. To clarify expression and regulation of this adipokine, apelin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in mouse 3T3-L1 adipocytes after treatment with various hormones known to induce insulin resistance. Interestingly, apelin synthesis was significantly upregulated by growth hormone (GH) and insulin in these cells whereas TNFalpha and isoproterenol did not have any effect. Thus, 500 ng/ml GH acutely induced apelin mRNA by up to 4-fold in a time-dependent fashion with significant stimulation seen at concentrations as low as 5 ng/ml effector. Furthermore, apelin secretion was assessed by enzyme-linked immunoassay in mouse adipocytes. Here, secretion of this adipokine was induced 2.85-fold by GH. Studies using pharmacological inhibitors suggested that the positive effect of GH on apelin mRNA synthesis is at least in part mediated by janus kinase 2 and phosphatidylinositol 3-kinase. Taken together, our results show a significant induction of apelin mRNA synthesis and protein secretion by GH.
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PMID:Growth hormone induces apelin mRNA expression and secretion in mouse 3T3-L1 adipocytes. 1712 24

Interest in the biology of white adipose tissue (WAT) has increased dramatically since the discovery of leptin in 1994. The identification of the product of the gene obese (ob) threw light on the role of adipose tissue in the physiopathology of obesity-related diseases, and spurred the identification of numerous other adipokines, many of a pro-inflammatory nature. It has become increasingly evident that WAT-derived cytokines mediate between obesity-related exogenous factors (nutrition and lifestyle) and the molecular events that lead to metabolic syndrome and inflammatory and/or autoimmune conditions. Here, we review recent adipokine research, with particular attention to the roles of leptin, adiponectin, resistin, visfatin, apelin, vaspin and hepcidin in such conditions.
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PMID:The emerging role of adipokines as mediators of inflammation and immune responses. 1750 80

It has been reported that apelin functions as an adipokine, which has been associated to obesity and insulin resistance. The objective of this study was to analyze the apelin mRNA expression in white adipose tissue (WAT) from high-fat (Cafeteria) fed rats, in order to examine potential relationships with obesity markers and other related risk factors. Animals fed on the high-fat diet during 56 days increased their body weight, total body fat and WAT depots weights when compared to controls. Apelin subcutaneous mRNA expression was higher in the Cafeteria than in the Control fed group and this increase was partially reversed by dietary vitamin C supplementation. Statistically significant associations between subcutaneous apelin gene expression and almost all the studied variables were identified, being of special interest the correlations found with serum leptin (r=0.517), liver malondialdehyde (MDA) levels (r=0.477), and leptin, IRS-3 and IL-1ra retroperitoneal mRNA expression (r=0.701; r=0.692 and r=0.561, respectively). These associations evidence a possible role for apelin in the excessive weight gain induced by high-fat feeding and increased adiposity, insulin-resistance, liver oxidative stress and inflammation.
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PMID:Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers. 1759 60

Adipokines, which are expressed and secreted from white adipose tissue (WAT), are potential factors that could contribute to the changes in energy homeostasis that occurs in pregnancy and lactation to meet the nutrient demands of fetal growth and milk production. The aim was to identify adipokines that could be involved by measuring the pattern of their mRNA expression in adipose tissue. Adipokine mRNAs were measured by quantitative RT-PCR in RNA isolated from white and brown adipose tissue (BAT) of rats at days 7, 14 and 21 of pregnancy, day 7 of lactation and virgin at dioestrus phase. The results for leptin, adiponectin and resistin expression in WAT essentially confirmed previous studies and it is unlikely that they are directly involved in the metabolic adaptations. The relative amounts of the mRNAs of the adipokines in BAT were comparable with those in WAT, but the patterns of expression did not follow those in WAT, except for apelin. Visfatin mRNA in WAT was elevated 2.5-fold only at day 21 of pregnancy. Apelin mRNA in WAT was increased 2.2-fold at day 7 of pregnancy. Retinol-binding protein 4 mRNA in WAT decreased to 46% of control at day 14 of pregnancy. Fasting-induced adipose factor (FIAF) mRNA in WAT was 2.2- to 2.5-fold higher throughout pregnancy and lactation. The marked induction of FIAF identifies this adipokine as a potential regulator of the metabolic adaptations that occur during pregnancy and lactation.
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PMID:Fasting-induced adipose factor identified as a key adipokine that is up-regulated in white adipose tissue during pregnancy and lactation in the rat. 1764 Dec 80

Interest in the biology of white adipose tissue has increased dramatically since the discovery of leptin in 1994. The identification of the product of the gene obese (ob) threw light on the role of adipose tissue in the physiopathology of obesity-related diseases and spurred the identification of numerous other adipokines, many of a proinflammatory nature. It has become increasingly evident that white adipose tissue-derived cytokines mediate between obesity-related exogenous factors (nutrition and lifestyle) and the molecular events that lead to metabolic syndrome, inflammation, and cardiovascular diseases. Here we review recent adipokine research, with particular attention to the roles of adiponectin, leptin, resistin, visfatin, apelin, omentin, and chemerin in such conditions.
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PMID:The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. 1802 38


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