Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population

https://doi.org/10.22146/ijbiotech.36975

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 prevent future risk of developing chronic diseases. 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 expression could explain the molecular mechanisms that occur in the early condition of IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the expression of genes that could potentially be an early marker of IR and NAFLD. All participants (n=21) were normolgycemic; 10 participants were categorized as healthy (without hepatosteatosis), 6 participants as having a higher risk of hepatosteatosis, and 5 participants as having hepatosteatosis. Gene expression analysis was performed using 2-ΔΔCT relative quantification method. There were significant differences on galnt2 (p<0.002) and sirt1 (p<0.010) expression between the first and the third tertile of HOMA-IR; and on ptpn1 (p<0.012) expression between the first and the second tertile of LFS. In conclusion, expression of galnt2 and sirt1 could be used as markers of the early condition of IR; while the expression of ptpn1 as early marker for NAFLD.


Keywords


galnt2; insulin resistance; NAFLD; ptpn1; sirt1



References

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.  6:33. 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. 13:146. 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 RA, Machmud R. 2002. Prevalence and risk factors for nonalcoholic fatty liver in Indonesia. J Gastroenterol Hepatol. 17(Suppl.): S154.

Hirata T, Higashiyama A, Kubota Y, Nishimura K, Sugiyama D, Kadota A, Nishida Y, Imano H, Nishikawa T, Miyamatsu N, Miyamoto Y, Okamura T. 2015. HOMA-IR 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. 2017. IDF Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes Federation. htpp://www.diabetesatlas.org.

[IDF] International Diabetes Federation. 2006. The IDF consensus worldwide definition of the Metabolic Syndrome. Brussels, Belgium: International Diabetes Federation. https://www.idf.org.

Kahl S, Strassburger K, Nowotny B, Livingstone R, Klu ̈ppelholz B, Keßel K, Hwang JH, Giani G, Hoffmann B, Pacini G, Gastaldelli A, Roden M. 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. 37:315-325. doi:10.4093/dmj.2013.37.5.315.

Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, Lundbom N, Rissanen A, Ridderstrale M, Groop L, Orho-Melander M, YKI-Jarvinen H. 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 realtime 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, Paola RD. 2013a. Role of GALNT2 in the modulation of ENPP1 expression, and insulin signaling and action.  Biochimica et Biophysica Acta. 1833:1388-1395. doi:10.1016/j.bbamcr.2013.02.032.

Marucci A, di Mauro L, Menzaghi C, Prudente S, Mangiacotti D, Fini G, Lotti G, Trischitta Trischitta, Paola RD. 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, Emeigh Hart SG, Burleson FG. 2018. 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, Md.] :[National Institutes of Health, National Heart, Lung, and Blood Institute].

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 BL, Jaisri G, Kumar KMP, Sharma R. 2011. Assessment of insulin resistance in normoglycemic young adults1. 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). Indones J Intern Med. 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):503–9. doi:10.1309/1PX2-LMPQ-UH1E-E12U.

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):e10. doi:10.4081/ejh.2011.e10.

Singh B, Saxena A. 2010. Surrogate markers of insulin resistance: a review. World J Diabetes 1(2): 36-47. doi: 10.4239/wjd.v1.i2.36.

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. 61:1415-1422. doi: 10.2337/db11-0744.

Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai W. 2007. Sirt1 improves insulin sensitivity under insulin-resistant conditions by repressing ptp1b. Cell Metab. 6:307-319. 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):263–273. 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):14230–41. doi:10.1074/jbc.M800061200



DOI: https://doi.org/10.22146/ijbiotech.36975

Article Metrics

Abstract views : 73

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 The Author(s)

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

The Indonesian Journal of Biotechnology (print ISSN 0853-8654; online ISSN 2089-2241) is published by the Research Center for Biotechnology in collaboration with the Graduate School of Universitas Gadjah Mada. The content of this website is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, and attributable to Siti Nurleily Marliana and Joaquim Baeta. Built on the Public Knowledge Project's OJS 2.4.8.1. Web
Analytics View website statistics.