Apelin Role in the Development of Glucose Metabolism Disorders (Review of the Literature and Our Own Researches)

G.V. Demidenko


The physiological and pathogenetic role of adipokine apelin, endogenous ligand of apelin (APJ or APLNR) receptors in the development of glucose metabolism disorders has been analyzed. Established correlations of apelin with components of carbohydrate metabolism confirm the effect on glucose metabolism manifestations. Ambiguous data about apelin level at insulin resistance syndrome, prediabetes, diabetes mellitus type 2, hypertension require further detailed study. The close association of apelin with development of diabetes mellitus type 2 and prediction of cardiovascular events in patients with metabolic syndrome has been found.


obesity; adipokines; apelin; cardiometabolic risk


Demydenko G., Kovalyova O. Apelins’ activity in patients with essential hypertension: age and gender peculiarities. Ukrayins'kyy kardiolohichnyy zhurnal. [Article in Ukrainian]. 2013:№6; 35-9.

Demydenko G.Apelin as a marker of insulin resistance in patients with essential hypertension. Sbornyk statey po materyalam XXVI mezhdunarodnoy nauchno-praktycheskoy konferentsyy «Sovremennaya medytsyna: aktual'nye voprosy», Novosybyrsk (Russia) [Article in Ukrainian]. 2013: 15-25.

Demydenko G. Insulineresistance and risk of type 2 diabetes development in patients with essential hypertension. Materyaly III Evrazyyskoho konhressv kardyolohov. [Article in Ukrainian] 2014: 102.

Kovalyova O. Prediabetes – diagnostic criteries and clinical values in cardiology. Zdorov’ya Ukrayiny. 2012; 1: 24-5.

Attane C., Daviaud D., Dray C., Dusaulcy R., Masseboeuf M., Prevot D., Carpene C., Castan-Laurell I., Valet P. Apelin stimulates glucose uptake but not lipolysis in human adipose tissue ex vivo.J. Mol. Endocrinol. 2011;46(1): 21–8.doi: 10.1677/JME-10-0105

Barnes G.,Japp A.G., Newby D.E.Translational promise of the apeline – APJ system. Heart. 2010; Vol. 96: 1011–16.doi: 10.1136/hrt.2009.191122

Boucher J.А, Masri B., le Daviaud D. et. al. Newly Identified Adipokine Up-Regulated by Insulin and Obesity. Endocrinology.

Castan-Laurell I., Dray C., Attané C. et al. Apelin, diabetes, and obesity. Endocrine. 2011;40 (1): 1–9.

Chen H., Zheng C., Zhang X. et al. Apelin alleviates diabetes-associated endoplasmic reticulum stress in the pancreas of akita mice. Peptides 2011;32 (8):1634–39.DOI:10.1016/j.peptides.2011.06.025

Chun H.J., ZA Ali, Y. Kojima et al. Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J Clin Invest. 2008;118(10): 3343–54.doi:10.1172/JCI34871.

Colwell J.A. Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome. JAMA. 2011; 306(2):215.doi:10.1001/jama.2011.970.

Demydenko G., Kovalyova O. Apelin as a marker of an insulinresistance in patients with essential hypertension. 16 th European Congress of Endocrinology 3-7 May 2014, Wroclaw (Poland). Endocrine Abstracts. 2014; (Vol 35): 193.

Demydenko G., Kovalyova O. Apelin expression in patients with essential hypertension and prediabetes. 23rd European meeting on hypertension and cardiovascular protection. Milan (Italy), June 14-17. 2013: P.323.

Demydenko G. Investigation of plasma apelin level in patients with essential hypertension corresponding to the type of obesity. Nauchnie vedomosty Belhorodskoho hosudarstvennoho unyversyteta «Medytsyna y farmatsyya». 2014; № 4 (175): 52-57.

Dray C., Knauf C., Daviaud D. et al. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell. Metab.2008; Vol. 8: 437–45.

Duparc T.Colom P. D., Cani T. Duparc, A. et al. Central apelin controls glucose homeostasis via a nitric oxide-dependent pathway in mice. Antioxidants and Redox Signaling. 2011; 6 (15):1477–96.DOI:10.1089/ars.2010.3454

Erdem G., Dogru T., Tasci I. et al. Low Plasma Apelin Levels in Newly Diagnosed Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2008; 116(5): 289-92.doi: 10.1055/s-2007-1004564.

Glassford A.J., Yue A.Y., Sheikh A.J., Glassford P. et al HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes. Physiol. Endocrinol. Metab. 2007; 293(6): 1590 – 96. PMCID:PMC2570255

Guo L., Li Q., Wang W., Yu Р. et al. Apelin inhibits insulin secretion in pancreatic β-cells by activation of PI3-kinase-phosphodiesterase 3B. Endocrine research. 2009; 34: 142-54. DOI:10.3109/07435800903287079

Higuchi K., Masaki T., Gotoh K., et al. Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice Endocrinology. 2007; 148(6): 2690–97. PMID:17347313

Ishida J., Hashimoto T., Hashimoto Y. et al. Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensinogen-type 1 receptor in blood pressure in vivo.J. Biol. Chem.2004; 279:26274-79.doi:10.1074/jbc.M404149200

Japp A.G., Cruden N.L., Amer D.A. et al. Vascular effects of apelin in vivo in man.J. Am. Coll.Cardiol. 2008;52: 908-13.doi: 10.1016/j.jacc.2008.06.013.

Kleinz M.J., Davenport A.P. Emerging roles of apelin in biology and medicine.Pharmacol. Ther. 2005;107 (2): 198–211. doi:10.1016/j.pharmthera.2005.04.001

Langelaan D.N., Bebbington E.M., Reddy T., Rainey J.K. Structural insight into G-protein coupled receptor binding by apelin. Biochemistry. 2009;48: 537-48.doi: 10.1021/bi801864b.

Leeper N. J.,Tedesco M. M., Kojima Y., et al. Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation.Am. J. Physiol. Heart. Circ. Physiol. 2009;296(5): 1329–35.doi: 10.1152/ajpheart.01341.2008

Li L.,Yang G., Li al. Changes and relations of circulating visfatin, apelin, and resistin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects. Exp. Clin. Endocrinol. Diabetes. 2006; 114: 544–48.

Margathe J.-F., Iturrioz X., Alvear-Perez R. et al. Structure–Activity Relationship Studies toward the Discovery of Selective Apelin Receptor Agonists. Journal of Medicinal Chemistry. 2014; 57 (7): 2908-19.

Mesmin C., Dubois M., Becher F. et al. Liquid chromatography/tandem mass spectrometry assay for the absolute quantification of the expected circulating apelin peptides in human plasma. Rapid.Commun. Mass Spectrom. 2010; Vol. 24 (19): 2875–84.DOI 10.1002/rcm.4718

Mesmin C., Fenaille F., Becher F. et al. Identification and characterization of apelin peptides in bovine colostrum and milk by liquid chromatography-mass spectrometry.J. Proteome Res. 2011;10(11):5222–31.DOI 10.1021/pr200725x

O’Shea M., Hansen M.J., Tatemoto K., Morris M.J. Inhibitory effect of apelin-12 on nocturnal food intake in the rat. Nutr. Neurosci. 2003; 6 (3): 163–7. PMID:12793520

Ouchi N., Parker J. L., Lugus J. J., Walsh K. Adipokines in inflammation and metabolic disease. Nat. Rewiews. Immunology.2011;11:85-97.doi: 10.1038/nri2921

Piya M.K.,McTernan P. G., Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J. of Endocrinology. 2013;216:1-15.

Przewlocka-Kosmala M., Kotwica T., Mysiak A., Kosmala W. Reduced circulating apelin in essential hypertension and its association with cardiac dysfunction. J. Of Hypertension. 2011; 5(29): 971–79.DOI: 10.1371/journal.pone.0093545

Ringstroem C., Nitert M.D., Bennet H. et al. Apelin is a novel islet peptide. Reg. Peptides.2010;162:44-51. doi:10.1006 j.regpep.2010.03.005

Rittig K., Hildebrandt U., Thamer C. et al. Apelin serum levels are not associated with early atherosclerosis or fat distribution in young subjects with increased risk for type 2 diabetes.J. Exper. Clin. Endocrinol. Diabetes. 2011;119 (6): 358–61.

Sawane M., Kajiya K., Kidoya H. et al. Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity. Diabetes. 2013; 62(6): 1970-80.doi: 10.2337/db12-0604

Sgourakis N.G., Bagos P.G., Hamodrakas S.J. Prediction of the coupling specificity of GPCRs to four families of G-proteins using hidden Markov models and artificial neural networks. Bioinformatics. 2005;21(22);4101–06.

Soriguer F., Garrido-Sanchez L., Garcia-Serrano S. et al. Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. Obesity Surgery. 2009;19 (11):1574–80.

Steinberg G.R., Kemp B. E. AMPK in Health and Disease. Physiol. Rev.2009;89(3):1025–78.DOI: 10.1152/physrev.00011.2008

Suzuki T., Imai J., Yamada T. et al. Interleukin-6 enchances glucose-stimulated insulin secretion from pancreatic β-cells: potential involvement of the PLC-IP3-dependent pathway. Diabetes.2011;60:537-47. doi: 10.2337/db10-0796.

Than A., ZhangX., Khee-ShingLeowM.Apelin Attenuates Oxidative Stress in Human adipocytes. Biol. Chem.2014; 289: 3763-74.doi: 10.1074/jbc.M113.526210

Wang G., KunduR., Han S. et al. Ontogeny of apelin and its receptor in the rodent gastrointestinal tract.Regul. Pept. 2009; 158 (1–3): 32–39. doi: 10.1016/j.regpep.2009.07.016

XuS.,TsaoP. S., Yue P. Apelin and insulinresistance: another arrow for the quiver? J. Diabetes. 2011; 3(3): 225 – 31.DOI:10.1016/j.regpep.2009.07.016

Yue P., JinH., Xu S. et al. Apelin decreases lipolysis via G(q), G(i), and AMPK-Dependent Mechanisms. Endocrinology.2011;152(1):59–68.doi: 10.1210/en.2010-0576

Yue P., JinH., Aillaud-Manzanera M. et al. Apelin is necessary for the maintenance of insulin sensitivity. Amer. J. Physiol. Endocrinol. Metab. 2009; 298: 59–67.doi: 10.1152/ajpendo.00385

Zhu S., Sun F., Li W. et al. Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes.Mol Cell Biochem.2011; 353(1-2): 305-313.Doi:10.1007/s11010 011 07990

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© "Publishing House "Zaslavsky", 1997-2019


   Seo анализ сайта