Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population
Eunice Limantara(1), Felicia Kartawidjajaputra(2*), Antonius Suwanto(3)
(1) Faculty of Biotechnology, Atma Jaya Catholic University, Jalan Jendral Sudirman 51, Jakarta Selatan 12930, Indonesia
(2) Nutrifood Research Center, PT Nutrifood Indonesia, Jalan Rawa Bali II No. 3, Jakarta Timur 13920, Indonesia
(3) Faculty of Biotechnology, Atma Jaya Catholic University, Jalan Jendral Sudirman 51, Jakarta Selatan 12930, Indonesia
(*) Corresponding Author
Abstract
Early detection of insulin resistance (IR) or non-alcoholic fatty liver disease (NAFLD) is crucial to preventing future risks of developing chronic diseases. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Liver Fat Score (LFS), and Fatty Liver Index (FLI) are generally employed to measure severity stages of IR and NAFLD. The study of gene expressions could explain the molecular mechanisms that occur early on in IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the gene expressions that could potentially be early markers of IR and NAFLD. All participants (n = 21) had normal blood glucose and were categorized as without hepatosteatosis (n = 10), at higher risk of hepatosteatosis (n = 6), and hepatosteatosis (n = 5). Gene expression analysis was performed using the 2-∆∆CT relative quantification method. There were significant differences in galnt2 (p < 0.002) and sirt1 (p < 0.010) expression between the first and the third tertiles of HOMA-IR; and in ptpn1 (p < 0.012) expression between the first and the second tertiles of LFS. In conclusion, the expressions of galnt2 and sirt1 could be used as early markers of IR, while the expression of ptpn1 could be employed as an early marker of NAFLD.
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Aragon G, Younossi ZM. 2010. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med. 77(3):195–204. doi:10. 3949/ccjm.77a.09064.
Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. 2006. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 6(1):33. doi:10.1186/1471-230x-6-33.
Du T, Yuan G, Zhang M, Zhou X, Sun X, Yu X. 2014. Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance. Cardiovasc Diabetol. 13(1):146. doi:10.1186/s12933-014-0146-3.
Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. 2013. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 5(5):1544–1560. doi:10. 3390/nu5051544.
Hasan I, Gani R, Machmud R, et al. 2002. Prevalence and risk factors for nonalcoholic fatty liver in indonesia. J Gastroenterol Hepatol. 17(Suppl A):30.
Hirata T, Higashiyama A, Kubota Y, Nishimura K, Sugiyama D, Kadota A, Nishida Y, Imano H, Nishikawa T, Miyamatsu N, et al. 2015. HOMAIR values are associated with glycemic control in japanese subjects without diabetes or obesity: the KOBE study. J Epidemiol. 25(6):407–414. doi:10. 2188/jea.je20140172.
[IDF] International Diabetes Federation. 2005. The IDF consensus worldwide definition of the metabolic syndrome. Technical report. International Diabetes Federation. Brussels.
[IDF] International Diabetes Federation. 2017. IDF diabetes atlas. 8th ed. Technical report. International Diabetes Federation. Brussels.
Kahl S, Straßburger K, Nowotny B, Livingstone R, Klüppelholz B, Keßel K, Hwang JH, Giani G, Hoffmann B, Pacini G, et al. 2014. Comparison of liver fat indices for the diagnosis of hepatic steatosis and insulin resistance. PLoS ONE. 9(4):e94059. doi:10.1371/journal. pone.0094059.
Kitada M, Koya D. 2013. SIRT1 in type 2 diabetes: mechanisms and therapeutic potential. Diabetes Metab J. 37(5):315–325. doi:10.4093/dmj.2013.37.5.315.
Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, Lundbom N, Rissanen A, Ridderstråle M, Groop L, et al. 2009. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 137(3):865–872. doi:10.1053/j.gastro.2009.06.005.
Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2- δδCT method. Methods. 25(4):402–408. doi: 10.1006/meth.2001.1262.
Marucci A, Cozzolino F, Dimatteo C, Monti M, Pucci P, Trischitta V, Di Paola R. 2013a. Role of GALNT2 in the modulation of ENPP1 expression, and insulin signaling and action: GALNT2: a novel modulator of insulin signaling. Biochim Biophys Acta Mol Cell Res. 1833(6):1388–1395. doi:10.1016/j.bbamcr.2013. 02.032.
Marucci A, Di Mauro L, Menzaghi C, Prudente S, Mangiacotti D, Fini G, Lotti G, Trischitta V, Di Paola R. 2013b. GALNT2 expression is reduced in patients with type 2 diabetes: possible role of hyperglycemia. PLoS ONE. 8(7):e70159. doi:10.1371/journal.pone. 0070159.
Mendrick DL, Diehl AM, Topor LS, Dietert RR, Will Y, La Merrill MA, Bouret S, Varma V, Hastings KL, Schug TT, et al. 2017. Metabolic syndrome and associated diseases: from the bench to the clinic. Toxicol Sci. 162(1):36–42. doi:10.1093/toxsci/kfx233.
[NCEP] National Cholesterol Education Program. 2001. ATP III guidelines at-a-glance quick desk reference. Bethesda: National Heart, Lung, and Blood Institute Bethesda.
Olokoba AB, Obateru OA, Olokoba LB. 2012. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 27(4):269–273. doi:10.5001/omj.2012.68.
Preethi B, Jaisri G, Kumar KP, Sharma R. 2011. Assessment of insulin resistance in normoglycemic young adults. Hum Physiol. 37(1):105–112. doi:10.1134/ s0362119711010154.
Purnamasari D, Soegondo S, Oemardi M, Gumiwang I. 2010. Insulin resistance profile among siblings of type 2 diabetes mellitus (preliminary study). Acta Med Indones. 42(4):204–208.
Sanderson SO, Smyrk TC. 2005. The use of protein tyrosine phosphatase 1B and insulin receptor immunostains to differentiate nonalcoholic from alcoholic steatohepatitis in liver biopsy specimens. Am J Clin Pathol. 123(4):503–509. doi:10.1309/ 1px2lmpquh1ee12u.
Singh B, Saxena A. 2010. Surrogate markers of insulin resistance: a review. World J Diabetes. 1(2):36. doi: 10.4239/wjd.v1.i2.36.
Song R, Xu W, Chen Y, Li Z, Zeng Y, Fu Y. 2011. The expression of sirtuins 1 and 4 in peripheral blood leukocytes from patients with type 2 diabetes. Eur J Histochem. 55(1). doi:10.4081/ejh.2011.e10.
Stull AJ, Wang ZQ, Zhang XH, Yu Y, Johnson WD, Cefalu WT. 2012. Skeletal muscle protein tyrosine phosphatase 1B regulates insulin sensitivity in African Americans. Diabetes. 61(6):1415–1422. doi:10.2337/ db11-0744.
Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q. 2007. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 6(4):307–319. doi:10.1016/j.cmet.2007.08. 014.
Wong RJ, Ahmed A. 2014. Obesity and non-alcoholic fatty liver disease: disparate associations among Asian populations. World J Hepatol. 6(5):263. doi: 10.4254/wjh.v6.i5.263.
Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, Kahn BB. 2008. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem. 283(21):14230–14241. doi:10.1074/jbc. m800061200.
DOI: https://doi.org/10.22146/ijbiotech.36975
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