Similar articles

Abstract: Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance in liver cirrhosis patients, we measured the insulin sensitivity index and determined the GLUT4 protein and mRNA contents of skeletal muscle by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal people and liver cirrhosis patients. The results showed that the levels of glucose, insulin, and C-peptide in two liver cirrhosis groups were higher and the insulin sensitivity index lower than those of the normal control group. The sensitivity of insulin may decrease with the decline of liver function. However, the contents of GLUT4 protein and mRNA in patients with advanced liver cirrhosis were similar to those of normal controls. In conclusion, insulin resistance is observed in patients with advanced liver cirrhosis but may not be correlated with the skeletal contents of GLUT4 protein and mRNA.

[1]Anty, R., Iannelli, A., Patouraux, S., Bonnafous, S., Lavallard, V.J., Senni-Buratti, M., Amor, I.B., Staccini-Myx, A., Saint-Paul, M.C., Berthier, F., et al., 2010. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients. Aliment. Pharmacol. Ther., 32(11-12):1315-1322.

[2]Arai, H., Awane, N., Mizuno, A., Fukaya, M., Sakuma, M., Harada, N., Kawaura, A., Yamamoto, H., Okumura, H., Taketani, Y., et al., 2010. Increasing early insulin secretion compensate adequately for hepatic insulin resistance in CCl₄-induced cirrhosis rats. J. Med. Invest., 57(1-2):54-61.

[3]Asano, T., Fujishiro, M., Kushiyama, A., Nakatsu, Y., Yoneda, M., Kamata, H., Sakoda, H., 2007. Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. Biol. Pharm. Bull., 30(9):1610-1616.

[4]Aytug, S., Reich, D., Sapiro, L.E., Bernstein, D., Begum, N., 2003. Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology, 38(6):1384-1392.

[5]Bragança, A.C., Álvares-da-Silva, M.R., 2010. Prevalence of diabetes mellitus and impaired glucose tolerance in patients with decompensated cirrhosis being evaluated for liver transplantation: the utility of oral glucose tolerance test. Arq. Gastroenterol., 47(1):22-27.

[6]Chang, L., Chiang, S.H., Saltiel, A.R., 2004. Insulin signaling and the regulation of glucose transport. Mol. Med., 10(7-12):65-71.

[7]Chen, X., Al-Hasani, H., Olausson, T., Wenthzel, A.M., Smith, U., Cushman, S.W., 2003. Activity, phosphorylation state and subcellular distribution of GLUT4-targeted Akt2 in rat adipose cells. J. Cell. Sci., 116(17):3511-3518.

[8]Holland-Fischer, P., Andersen, P.H., Lund, S., Pedersen, S.B., Vinter-Jensen, L., Nielsen, M.F., Kaal, A., Dall, R., Schmitz, O., Vilstrup, H., 2007. Muscle GLUT4 in cirrhosis. J. Hepatol., 47(2):212-219.

[9]Huang, S., Czech, M.P., 2007. The GLUT4 glucose transporter. Cell Metab., 5(4):237-252.

[10]Hung, C.H., Wang, J.H., Hu, T.H., Chen, C.H., Chang, K.C., Yen, Y.H., Kuo, Y.H., Tsai, M.C., Lu, S.N., Lee, C.M., 2010. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J. Gastroenterol., 16(18):2265-2271.

[11]Jessen, N., Buhl, E.S., Schmitz, O., Lund, S., 2006. Impaired insulin action despite upregulation of proximal insulin signaling: novel insights into skeletal muscle insulin resistance in liver cirrhosis. J. Hepatol., 45(6):797-804.

[12]Kimura, Y., Hyogo, H., Ishitobi, T., Nabeshima, Y., Arihiro, K., Chayama, K., 2011. Postprandial insulin secretion pattern is associated with histological severity in non-alcoholic fatty liver disease patients without prior known diabetes mellitus. J. Gastroenterol. Hepatol., 26(3):517-522.

[13]Kirwan, J.P., Solomon, T.P., Wojta, D.M., Staten, M.A., Holloszy, J.O., 2009. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus. Am. J. Physiol. Endocrinol. Metab., 297(1):151-156.

[14]MacLaren, R., Cui, W., Simard, S., Cianflone, K., 2008. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue. J. Lipid Res., 49(2):308-323.

[15]Maier, V.H., Gould, G.W., 2000. Long term insulin treatment of 3T3-L1 adipocytes results in mis-targeting of GLUT4: implications for insulin-stimulated glucose transport. Diabetologia, 43(10):1273-1281.

[16]Malik, S.M., Ahmad, J., 2010. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl., 16(4):533.

[17]Matsumoto, D., Yamanaka-Okumura, H., Arai, H., Sakuma, M., Yamamoto, H., Taketani, Y., Tani, Y., Morine, Y., Shimada, M., Takeda, E., 2007. Nutritional treatment of a patient with hepatic cirrhosis with the novel low glycemic index liquid food. J. Med. Invest., 54(3-4):375-380.

[18]Ng, Y., Ramm, G., Lopez, J.A., James, D.E., 2008. Rapid activation of Akt2 is sufficient to stimulate GLUT4 translocation in 3T3-L1 adipocytes. Cell Metab., 7(4):348-356.

[19]Peck, G.R., Chavez, J.A., Roach, W.G., Budnik, B.A., Lane, W.S., Karlsson, H.K., Zierath, J.R., Lienhard, G.E., 2009. Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation. J. Biol. Chem., 284(44):30016-30023.

[20]Petrides, A.S., Groop, L.C., Riely, C.A., de Fronzo, R.A., 1991. Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. J. Clin. Invest., 88(2):561-570.

[21]Petrides, A.S., Stanley, T., Matthews, D.E., Vogt, C., Bush, A.J., Lambeth, H., 1998. Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia normalizes insulin sensitivity. Hepatology, 28(1):141-149.

[22]Ramm, G., Larance, M., Guilhaus, M., James, D.E., 2006. A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. J. Biol. Chem., 281(39):29174-29180.

[23]Singal, A.K., Ayoola, A.E., 2008. Prevalence and factors affecting occurrence of type 2 diabetes mellitus in saudi patients with chronic liver disease. Saudi J. Gastroenterol., 14(3):118-121.

[24]Suárez, E., Bach, D., Cadefau, J., Palacin, M., Zorzano, A., Gumá, A., 2001. A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells. J. Biol. Chem., 276(21):18257-18264.

[25]Yip, M.F., Ramm, G., Larance, M., Hoehn, K.L., Wagner, M.C., Guilhaus, M., James, D.E., 2008. CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes. Cell Metab., 8(5):384-398.