2型糖尿病患者血浆apelin-12水平与高血压、胰岛素抵抗相关因素的研究
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摘要
目的:探讨apelin-12与胰岛素抵抗(IR)、原发高血压、肥胖、炎症等的相关性。
方法:测定31例2型糖尿病(T2DM)、37例2型糖尿病合并高血压患者(T2DMH)及25例健康对照者血浆apelin-12、肿瘤坏死因子α(TNF-α)、血脂、空腹胰岛素(FINS)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、体重指数(BMI)等水平并进行各参数之间的相关分析。
结果:①T2DMH组血浆apelin-12水平低于NGT组和T2DM组(P<0.05或P<0.01),T2DM组血浆apelin-12水平高于NGT组(P<0.05)。②T2DMH组TNF-α水平高于T2DM组和NGT组(P<0.05或者P<0.01),T2DM组TNF-α水平高于NGT组(P<0.05)③直线相关分析显示,空腹血浆apelin-12与腰臀比(WHR), HOMA-IR,FINS,收缩压(SBP),TNF-α,甘油三酯(TG)呈负相关,与HDL-C呈正相关。多元逐步回归分析提示:WHR、HOMA-IR、TG、TNF-α是血浆apelin-12的独立相关因素。
结论:血浆apelin-12水平在T2DM组升高,在T2DMH组降低,它与肥胖、IR、炎症等相关。推测apelin-12可能参与了IR、T2DM、原发性高血压等疾病的发生发展。
Objective: To investigate the correlation of plasma apelin-12 level and hypertension、obesity、insulin resistance、inflammation.
Methods: 31 T2DM patients, 37 T2DM complicated with hypertension patients and 25 healthy controls were studied. The plasma level of apelin-12、tumor necrosis factor-α(TNF-α)、blood fat、glycosylated hemoglobin(HbA1c)、fasting plasma glucose、fasting insulin level、insulin resistance index(HOMA-IR)、body mass index(BMI) and blood pressure were measured in all subjects. The correlation of these parameters were analyzed.
Results:①The apelin-12 levels in patients with T2DM complicated by hypertension were significantly lower compared with normal controls and those with T2DM only(P<0.05orP<0.01),the apelin-12 level of patients with T2DM were higher than those in control group (P<0.05).②The TNF-αlevels in patients with T2DM and hypertension were significantly higher compared with the control group and those with T2DM (P<0.05orP<0.01),the TNF-αlevel of patients with T2DM only were significantly higher than those in control group(P<0.05).③The variable correlations showed a negative correlation between the plasma apelin-12 level and WHR、FINS、HOMA-IR、TG、SBP、TNF-α,a positive correlation between it and the HDL-C. Multiple regression showed WHR、HOMA-IR、TG、TNF-αwere equal predicators of plasma apelin-12 level.
Conclusion: The plasma level of apelin-12 increased in the group of T2DM and decreased in the group of T2DM with hypertension.Apelin-12 is correlated with obesity、insulin resistance and inflammation. A speculation can be drew that the apelin-12 may contribute to the development of IR、T2DM and hypertension.
方法:测定31例2型糖尿病(T2DM)、37例2型糖尿病合并高血压患者(T2DMH)及25例健康对照者血浆apelin-12、肿瘤坏死因子α(TNF-α)、血脂、空腹胰岛素(FINS)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、体重指数(BMI)等水平并进行各参数之间的相关分析。
结果:①T2DMH组血浆apelin-12水平低于NGT组和T2DM组(P<0.05或P<0.01),T2DM组血浆apelin-12水平高于NGT组(P<0.05)。②T2DMH组TNF-α水平高于T2DM组和NGT组(P<0.05或者P<0.01),T2DM组TNF-α水平高于NGT组(P<0.05)③直线相关分析显示,空腹血浆apelin-12与腰臀比(WHR), HOMA-IR,FINS,收缩压(SBP),TNF-α,甘油三酯(TG)呈负相关,与HDL-C呈正相关。多元逐步回归分析提示:WHR、HOMA-IR、TG、TNF-α是血浆apelin-12的独立相关因素。
结论:血浆apelin-12水平在T2DM组升高,在T2DMH组降低,它与肥胖、IR、炎症等相关。推测apelin-12可能参与了IR、T2DM、原发性高血压等疾病的发生发展。
Objective: To investigate the correlation of plasma apelin-12 level and hypertension、obesity、insulin resistance、inflammation.
Methods: 31 T2DM patients, 37 T2DM complicated with hypertension patients and 25 healthy controls were studied. The plasma level of apelin-12、tumor necrosis factor-α(TNF-α)、blood fat、glycosylated hemoglobin(HbA1c)、fasting plasma glucose、fasting insulin level、insulin resistance index(HOMA-IR)、body mass index(BMI) and blood pressure were measured in all subjects. The correlation of these parameters were analyzed.
Results:①The apelin-12 levels in patients with T2DM complicated by hypertension were significantly lower compared with normal controls and those with T2DM only(P<0.05orP<0.01),the apelin-12 level of patients with T2DM were higher than those in control group (P<0.05).②The TNF-αlevels in patients with T2DM and hypertension were significantly higher compared with the control group and those with T2DM (P<0.05orP<0.01),the TNF-αlevel of patients with T2DM only were significantly higher than those in control group(P<0.05).③The variable correlations showed a negative correlation between the plasma apelin-12 level and WHR、FINS、HOMA-IR、TG、SBP、TNF-α,a positive correlation between it and the HDL-C. Multiple regression showed WHR、HOMA-IR、TG、TNF-αwere equal predicators of plasma apelin-12 level.
Conclusion: The plasma level of apelin-12 increased in the group of T2DM and decreased in the group of T2DM with hypertension.Apelin-12 is correlated with obesity、insulin resistance and inflammation. A speculation can be drew that the apelin-12 may contribute to the development of IR、T2DM and hypertension.
引文
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7.吴哲兵,余静,李光迪,等.替米沙坦对高血压病患者血浆apelin-1 2水平的影响.临床荟萃2006,21(21)1530-1532.
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4. Sorhede Winzell M,Magnusson C,Ahren B.The apj receptor is expressed in pancreatic islet and its ligand,apelin,inhibits insulin secretion in mice. Regul Pept,2005,131:12-17.
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6.魏丽,贾伟平,吴海娅,等.肥胖及2型糖尿病患者血清apelin水平及其相关因素分析.中华内分泌代谢杂志,2007,23(2)130-133.
7.吴哲兵,余静,李光迪,等.替米沙坦对高血压病患者血浆apelin-1 2水平的影响.临床荟萃2006,21(21)1530-1532.
8. O’Shea M ,Hansen M J,Tatemoto K,et a1.Inhibitory effect of apelin-12 on nocturnal food intake in the rat.Nutr Neurosci,2003,6:163—167.
9. Sunter D,Hewson A K。Dickson S L. Intracerebroventricular injection of apelin-12 reduces food intake in the rat.NeurosciLett,2003,353:1-4.
10. Taheri S,Murphy K ,Cohen M ,et a1.The effects of centrally administered apelin-13 on food intake , water intake and pituitary hormone release in rats. Biochem Biophys Res Cornmum,2002,291:1208—1212
11. O’Shea M ,Hansen M J,Tatemoto K,et a1.Inhibitory effect of apelin-12 on nocturnal food intake in the rat.Nutr Neurosci,2003,6:163—167.
12. Wang G ,Anini Y,Wei W ,et a1. Apelin,a new enteric peptide:localization in the gastrointestinal tract, ontogeny,andstimulation of gastric eel1 proliferationand of cholecystokinin secretion. Endocrinology,2004,145:1342—1348.
13. Boucher J,Masri B,Daviaud D,et a1.Apelin,a newly identified adipokine up-regulated by insulin and obesity. Endocrinology,2005,146:1764—1771
14. W ei L,Hou X,Tatemoto K.Regulation of apelin m RNA expression by insulin and glucocorticoids in mouse 3T3一L1 adipocytes. Regul Pept,2005,I32:27—32.
15. Heinonen M V ,Purhonen A K ,Miettinen P, et a1. Apelin,orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding.Regul Pept,2005,130:7-13.
16.付研.高血压与胰岛素抵抗.中国临床医生, 2008,36 (9)13-15.
17. Ishida J,Hashimoto T.Regulatory roles for APJ a seventrasmembrane receptor related to angiotension——type I receper in blood pressuer in vivo[J].J Biol Chem,2004,279(26):274—279
18. Zhong JC,Yu XY,Huang Y,et a1.Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice.Cardiovasc Res,2007,74:388—395.
19. Szokodi I,Tavi P,F/ildes G ,et a1.Apelin,the novel endogenous ligand of the orphan receptor APJ,regulates cardiac contractility. Cire Res,2002,91(5):434—440.
20. Ashley EA,Powers J,Chen M,et a1.The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo.Cardiovasc Res,2005,65(1):73—82.
21. Berry MF,Pirolli TJ,Jayasankar V,et a1.Apelin has in vivo inotropie efects on normal and failing hearts.Circulation,2004,110(11 Suppl 1):II187—193.
22. Chen MM ,Ashley EA,Deng DX,et a1.Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction.Circulation,2003,108(12):l432—1439
23. Kagiyama S,Fukuhara M.Matsumura K,et a1.Central and peripheral card iovascular actions of apelin in conscious rats.Regul Pept,2005,125(1/3):55—59.
24. Tatemoto K, Takayama K,Zou MX,et a1.Th e novel peptide apelin lowers blood pressure via a nitric oxide—dependent mechanism.Regul Pept,2001,99(2/3):87—92.
25. Zhong JC,Huang DY,“u GF,et a1.Efects of all—trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats.Cardiovasc Res,2005,65(3):743—750.
26. Azizi M,Iturrioz X,Blanchard A,et a1.Reciprocal regulation of plasma apelin and vasopressin by osmotic stimuli[J].JAm Soc Nephrol,2008;13(6):422—432.
27. Iturrio ZX,Eimessari S,Demota N,et a1.Functional dissociation between apelin receptor signaling and endocytosis:implications for the efects of apelin on arterialblood pressure[J].Archmal,2007,100(8):704-708.
28. Hashimoto T,Kihara M,Ishida J,et a1.Apelin stimulates myosin light chain phosorylation in vascular smooth muscle cells[J].Arterizoscler Thromb Vasc Biol,2006,26(6):126—127.
29. Aggarwal BB.Tumour necrosis factors receptor associated signalling tooleeules and their role in activation of apoptosis,JNK and NF—kappaB[J].Ann Rheum Dis,2000;59(Suppl 1):6-16.
30. Powell DJ,Hajduch E,Kular G,et a1.Ceramide disables 3-pbosphoinositide binding to the pleckstrin homology domain of protein kinase B (PKB)/Akt by a PKCzeta—dependent mechanism[J].Mol Cell Bid,2003:23(21):7794—808.
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