Molecular properties of apelin: tissue distribution and receptor binding

Kawamata, Yuji; Habata, Yugo; Fukusumi, Shoji; Hashimoto, Masaki; Fujii, Ryo; Hinuma, Shuji; Nishizawa, Naoki; Kitada, Chieko; Onda, Haruo; Nishimura, Osamu; Fujino, Masahiko

doi:10.1016/s0167-4889(00)00143-9

Cited by 451 publications

(323 citation statements)

References 18 publications

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“…Results are representative of those obtained from three independent experiments. localization of apelin expression in tissues was observed in vascular endothelial cells (ECs), adipose tissue and epithelial cells, suggesting a role for apelin/APJ in angiogenesis and vascular formation [18,19]. Similarly, location of APJ is very important for Apelin/APJ signaling pathway to exert physiological function in various cells and tissues [20].…”

Section: Discussionmentioning

confidence: 99%

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Chen

Tao

Jiang

2015

Sci. China Life Sci.

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Section: Discussionmentioning

confidence: 99%

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Chen

Tao

Jiang

2015

Sci. China Life Sci.

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“…Overall, apelin and APJ mRNA transcripts and respective peptides, are abundantly present in central nervous system and also in peripheral tissues such as vascular endothelium, heart, lung, kidney and mammary gland [18,25,40,32,10,21], suggesting a functional role of apelin/APJ in these tissues. Remarkably the bulk of the studies report cardiovascular actions of apelin/APJ.…”

Section: Introductionmentioning

confidence: 99%

The apelinergic system in the developing lung: Expression and signaling

et al. 2011

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a b s t r a c tApelin and its receptor APJ constitute a signaling pathway best recognized as an important regulator of cardiovascular homeostasis. This multifunctional peptidergic system is currently being described to be involved in embryonic events which extend into vascular, ocular and heart development. Additionally, it is highly expressed in pulmonary tissue. Therefore, the aim of this study was to investigate the role of apelinergic system during fetal lung development. Immunohistochemistry and Western blot analysis were used to characterize apelin and APJ expression levels and cellular localization in normal fetal rat lungs, at five different gestational ages as well as in the adult. Fetal rat lung explants were cultured in vitro with increasing doses of apelin. Treated lung explants were morphometrically analyzed and assessed for MAPK signaling modifications. Both components of the apelinergic system are constitutively expressed in the developing lung, with APJ exhibiting monomeric, dimeric and oligomeric forms in the pulmonary tissue. Pulmonary epithelium also displayed constitutive nuclear localization of the receptor. Fetal apelin expression is higher than adult expression. Apelin supplementation inhibitory effect on branching morphogenesis was associated with a dose dependent decrease in p38 and JNK phosphorylation. The results presented provide the first evidence of the presence of an apelinergic system operating in the developing lung. Our findings also suggest that apelin inhibits fetal lung growth by suppressing p38 and JNK signaling pathways.

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“…However, multiple apelin forms exist consisting of 13, 16 and 17 amino acids with the C-terminal end identical in all forms (13); in fact, the C-terminal end is highly conserved across species (5).…”

Section: Introductionmentioning

confidence: 99%

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

Winzell

Magnusson

Åhrén

2005

Regulatory Peptides

175

107

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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 (1g/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 (2nmol/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 µmol/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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Molecular properties of apelin: tissue distribution and receptor binding

Cited by 451 publications

References 18 publications

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

The apelinergic system in the developing lung: Expression and signaling

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

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