丙型肝炎病毒感染致糖代谢异常的相关机制研究进展

doi:10.3969/j.issn.1672-5069.2014.01.033

摘要/Abstract

摘要： 丙型肝炎病毒感染者糖代谢异常的发病率有不同程度的升高。除了肝源性糖尿病共有的发病机制外,胰岛β细胞功能的减低和胰岛素抵抗（IR）在丙型肝炎病毒感染者糖代谢异常的发病机制中起着重要作用。但IR可能更为重要,而肝脂肪变性、肿瘤坏死因子-α过表达、脂联素水平下降、细胞因子信号抑制因子合成以及铁代谢异常等都可能参与了IR的形成。

关键词: 慢性丙型肝炎, 糖尿病, 胰岛素抵抗, 核因子-κ, B

Abstract: The morbidity of abnormal glucose metabolism in patients with hepatitis C infection increases gradually. In addition to the common pathogenesis similar to hepatogenous diabetes,malfunciton in pancreatic β-cell and insulin resistance （IR） play important roles in the pathogenesis of abnormal glucose metabolism in patients with hepatitis C virus infection. IR may be more important,and hepatic steatosis, tumor necrosis factor-α overexpression,decreased adiponectin, abnormality in synthesis of cytokine signaling inhibitory factors and in iron metabolism may all be involved in IR.

Key words: Choronic hepatitis C, Diabetes, Insuline resitence, Nuclear factor-κ, B

康姚洁综述, 王煊审校. 丙型肝炎病毒感染致糖代谢异常的相关机制研究进展[J]. 实用肝脏病杂志, 2014, 17(1): 102-105.

Kang Yaojie, Wang Xuan. Progress in mechanisms of abnormal glucose metabolism in patients with hepatitis C virus infection[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2014, 17(1): 102-105.

参考文献

[1] Pazhanivel M,Jayanthi V. Diabetes mellitus and cirrhosis liver. Minerva Gastroenterol Dietol,2010,56（1）：7-11.
[2] Knobler H,Schihmanter R,Zifroni A,et al.Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection. Mayo Clin Proc,2000,75（4）：355-359.
[3] Jacobson IM,Cacoub P,Dal Maso L,et al. Manifestations of chronic hepatitis C virus infection beyond the liver.Clin Gastroenterol Hepatol,2010,8（12）：1017-1029.
[4] Saltierl AR,Kahn CR.Insulin signalling and the regulation of glucose and lipid metabolism. Nature,2001,414（6865）：799-806.
[5] Shintani Y,Fujie H,Miyoshi H,et al.Hepstitis C virus infection and diabetes：direct involvement of the virus in the development of insulin resistance. Gastroenterology,2004,126（3）：840-848.
[6] Aytug S,Reich D,Sapiro LE,et al. Impaired IRS-1/PI3-kinase signaling in patients with HCV：am echanism for increased prevalence of type 2 diabetes. Hepatology,2003,38（6）：1384-1392.
[7] Trpkovic A,Stokic E,Radak,et al. Chronic hepatitis C infection,insulin resistance and vascular disease. Curr Pharm Des, 2010,16（34）：3823-3829.
[8] Jacobson I M,Cacoub P,Dal Maso L,et al. Manifestations of chronic hepatitis C virus infection beyond the liver. Clin Gastroenterol Hepatol,2010,8（12）：1017-1029.
[9] Garcia Compean D,Jaquez Qintana JO,Gonzale JA,et al.Liver cirrhosis and diabetes：risk factors,pathophysiology,clinical implications and management. World J Gastroenterol,2009,15（3）：280-288.
[10] Picardi A,D’Avola D,Gentilucci UV,et al. Diabetes in chronic liver diseas：from old concepts to new evidence. Diabetes Metab Res Rev,2006,22：274-283.
[11] Thomssen R,Bonk S,Profe C,et al. Association of hepatitis C virus in human sera with beta-lipoprotein. Med Micobiol Immunol, 1992,181：293-300.
[12] Asselah T,Rubbia- Brandt L,Marcellin P,et al.Steatosis in chronic hepatitis C：why dose it really matter. Gut,2006,55：123-130.
[13] Perlemuter G,Sabile A,Letteron P,et al.Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion：a model of viral- related steatosis. Faseb J,2002,16（2）：185-194.
[14] Yoon EJ,Hu KQ.Hepatitis C virus （HCV） infection and hepatic steatosis.Int J Med Sci,2006,3：53-56.
[15] Sanyal AJ. Review article： non-alcoholic fatty liver disease and heaptitis C risk factora and clinical implications. Aliment Pharmacol Ther,2005,22（2）：48-51.
[16] Noto H,Raskin P. Hepatitis C infection and diabets. Diabetes Complications,2006,20（2）：113-120.
[17] Kim KH,Hong SP,Kim K,et al. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARgamma. Biochem Biophys Res Commun,2007,355（4）：883-888.
[18] Cai DS,Yuan MS,Daniel F,et al. Local and systemic insulin resistance resulting from hepatic activation of IKK -β and NF-κB. Nat Med,2005,11（2）：183.
[19] Matsuda M,Kawasaki F,Yamada K,et al. Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese type 2 diabetic subjects. Diabet Med,2004,21：881-888.
[20] Pawlak K,Mysliwiec M,Pawla D. Chronic viral hepatitis and iron affect the plasma levels of LIGHT-a new member of the TNF super family in uremic haemodialyzed patients. Cytokine,2007,39：201-206.
[21] Knobler H,Schattner A. TNF-α,chronic hepatit is C and diabetes：a novel triad. QJM,2005,98（1）：1-6.
[22] Sheikh MY,Choi J,Qadri I,et al. Hepatitis C virus infection： molecular pathways to metabolic syndrome. Hepatology,2008,47（6）：2127- 2133.
[23] Neuman MG,Benhamou JP,Malkiewicz IM,et al. Kinetics of serum cytokines reflects changes in the severity of chronic hepatitis C presenting minimal fibrosis. J Viral Hepat,2002,9（2）：134-140.
[24] Greenberg AS,Mc Daiel ML. Identifying the inks between obesity,insulin resistance and cell function：potential role of adipocytederived cytokines in the pathogenesis of type 2 diabete. Eur J Clin Invest,2002,32（3）：24-34.
[25] Wolf AM,Wolf D,Avila MA,et al. Up-regulation of the anti-inflammatory adipokine adiponect in acute liver failure in mice. J Hepatol,2006,44（3）：537-543.
[26] Yamauchi T,Kamon J,Ito Y,et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003, 423（6941）：762-769.
[27] Yamauchi T,Nio Y,Maki T,et al. Targeted disruption of AdipoR1 and AdipoR 2 causes abrogation of adiponectin binding and metabolic action. Nat Med,2007,13（3）：332-339.
[28] Yamauchi T,Kamon J,Waki H,et al.Globnular adiponectin protected ob/ob mice from diabetes and ApoE-deficinet-mice from atheroscrosis. J Biol Chem,2003,278（4）：2461-2468.
[29] Kadowaki T,Yamauehi T. Adiponectin and adiponectin receptors. Endoer Rev,2005,26（3）：439-451.
[30] 崔丽娟,都健,曾芙蓉,等. 胰岛素抵抗大鼠脂联素与IKKmRNA表达的相关性研究. 中国医科大学学报,2007,6（36）： 694-696.
[31] Lappas M,Permezel M,Rice GE.Leptin and adiponectin stimulate the release of proinfla mmatory cytokines and prostaglandins from human placenta and maternal adipose tissue via NF-kappaB, PPAR-gamma and ERK1/2. Endocrinolgy,2005,146（8）：3334-3342.
[32] Petit JM,Minello A,Jooste V,et al .Decreased plasma adiponectin concentrations are closely related to steatosis in hepatitis C virus infected patients. J Clin Endocrinol Metab,2005,90（4）：2240-2243.
[33] Liu CJ,Chen PJ,Jeng YM,et al. Serum ad iponect in correlates with viral characteristics but not histologic features in patients with chronic hepatitis C. J Hepatol,2005,43（2）： 235-242.
[34] Roblin X,Chevassus P,Boudenaghe T,et al. Should the insulin resistance associated with hepatic iron overload be researched during diabetes mellitus type 2. Diabetes and Metabolism,2002,28（4）：335-339.
[35] D'souza RF,Feakins R,Mears L,et al. Relationship between serum ferritin,hepatic iron staining,diabetes mellitus and fibrosis progression in patients with chronic hepatitis C. Aliment Pharmacol Ther,2005,21（5）：519-524.
[36] Ueki K,Kondo T,Kahn CR,et al.S uppressor of cytok inesignaling 1（SOCS-1） and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphory lation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol,2004,24：5434-5446.