Selenium Supplementation Increases Hepatic Glucose-6-Phosphatase and Peroxisome Proliferator Activated Receptor Gamma Coactivator-1α Activity in Male Wistar Rats

Abstract

Increased selenium supplementation has been implicated in diabetes mellitus via peroxisome-proliferator-activated-receptor-gamma-coactivator-1-alpha (PGC-1α) associated pathways. This study was designed to investigate the effect of selenium supplementation on PGC-1α and glucose-6-phosphatase (G6Pase) as well its likely hepato toxicity in male Wistar rats. Animals were randomly divided into 3 groups (n=10/group) and treated orally with water (0.2ml - group 1) or selenium (25µg/day -group 2; 50µg/day - group 3) for 28 and 56days, respectively. Thereafter, blood samples were collected and estimated for glucose, alkaline-phosphate (ALP), gamma-glutamyltransferase (GGT) and aspartate-aminotransferase (AST). Liver homogenates were analyzed for PGC-1α and G6Pase activity. Significant dose-dependent increases in blood glucose, hepatic PGC-1α and G6Pase activities were observed on days 28 and 56 in selenium groups compared to group 1. Serum GGT activity increased in both selenium groups on day 28 however, on day 56 values in group 2 were reduced and increased in group 3, respectively. Compared to control ALP reduced in selenium groups while AST was not significantly different. This study suggests that selenium supplementation increases hepatic peroxisome-proliferator-activated-receptor-gamma-coactivator-1α and glucose-6-phosphatase activity leading to a likely increase in hepatic glucose output. It also shows that though selenium supplementation at the doses used maybe nontoxic to hepatocytes, it may however exert potential toxicity on the biliary tract

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References

Ayaz, M., Ozdemir, S., Yaras, N., Vassort, G., Turan, B., 2005.Selenium-induced alterations in ionic currents of rat cardiomyocytes.Biochemical and Biophysical Research Communications, 327, 163–173. doi: 10.1016/j.bbrc.2004.12.003.

Barham, D, Trinder, P., 1972.An improved colour reagent for the determination of blood glucose by the oxidase system.Analyst. 97 (151), 142-5.

Gernand, A.D., Schulze, K.J., Stewart, C.P., West, K.P.Jr, Christian, P., 2016. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nature Reviews Endocrinology, 12 (5), 274–289. doi:10.1038/nrendo.2016.37.

Ghosh, A., Shieh, J.J., Pan, C.J., Sun, M.S., Chou, J.Y., 2002. The catalytic center of glucose-6-phosphatase. HIS176 is the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis. The Journal of Biological Chemistry 277 (36), 32837–42. doi:10.1074/jbc.M201853200.

Hawkes, W.C., Keim, N.L., 2003. Dietary Selenium Intake Modulates Thyroid Hormone and Energy Metabolism in Men. Journal of Nutrition 133 (11), 3443–3448.

Huang, Z., Rose, A.H., Hoffmann, P.R., 2012. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxidants and Redox Signaling,16 (7), 705–743. doi:10.1089/ars.2011.4145.

Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.

Ishikura K, Misu H, Kumazaki M, Takayama H, Matsuzawa-Nagata N, Tajima N, Chikamoto K, Lan F, Ando H, Ota T, Sakurai M, Takeshita Y, Kato K, Fujimura A, Miyamoto K, Saito Y, Kameo S, Okamoto Y, Takuwa Y, Takahashi K, Kidoya H, Takakura N, Kaneko S, Takamura T. Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells. Diabetologia. 2014, 57(9): 1968 -76. doi: 10.1007/s00125-014-3306-9.

Johnson, C.C., Fordyce, F.M., Rayman, M.P., 2010. Symposium on ‘Geographical and geological influences on nutrition’: factors controlling the distribution of selenium in the environment and their impact on health and nutrition. Proceedings of the Nutritional Society, 69 (1), 119-32.doi: 10.1017/S0029665109991807.

Kang B.P.S., Mehta U., Bansal M.P., 2001. Selenium supplementation protects from high fat diet-induced atherogenesis in rats: role of mitogen stimulated lymphocytes. Indian Journal of Experimental Biology, 2001, 39 (8), 793-7

Koide, H. and Oda T., 1959. Pathological occurrence of glucose-6-phosphatase in serum in liver diseases.ClinicaChimicaActa, 4, 554-561.

Koo, S. H., Satoh H., Herzig S., Lee C. H., Hedrick S., Kulkarni R., Evans R. M., Olefsky J., Montminy M., 2004. PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nature Medicine 10 (5): 530–534

Liang,Huiyun, Ward, Walter F., 2006. PGC-1: a key regulator of energy metabolism. Advances in Physiology Education,30, 145–151.doi:10.1152/advan.00052.2006.

Lum. G, Gambino, S.R., 1972. Serum Gamma-GlutamylTranspeptidase Activity as an Indicator of Disease of Liver, Pancreas, or Bone. Clinical Chemistry, 18(4), 358-62.

McClung JP, Roneker CA, Mu W, Lisk DJ, Langlais P, Liu F, Lei XG. Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proc Natl Acad Sci. 2004;101(24):8852-7.

Mehdi, Y., Hornick, J.L., Istasse, L., Dufrasne, I., 2013. Selenium in the environment, metabolism and involvement in body functions. Molecules, 18, 3292-3311.doi: 10.3390/molecules18033292

Mehta, S.L., Kumari, S., Mendelev, N., Li, P.A., 2012. Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neuroscience, 13:79. doi:10.1186/1471-2202-13-79

Misu H, Takamura T, Takayama H, Hayashi H, Matsuzawa-Nagata N, Kurita S, Ishikura K, Ando H, Takeshita Y, Ota T, Sakurai M, Yamashita T, Mizukoshi E, Yamashita T, Honda M, Miyamoto K, Kubota T, Kubota N, Kadowaki T, Kim HJ, Lee IK, Minokoshi Y, Saito Y, Takahashi K, Yamada Y, Takakura N, Kaneko S. A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab. 2010 12(5): 483-95. doi: 10.1016/j.cmet.2010.09.015.

Ogawa-Wong, A.N., Berry, M.J., Seale, L.A., 2016. Selenium and Metabolic Disorders: An Emphasis on Type 2 Diabetes Risk. Nutrients, 8(2), 80. doi:10.3390/nu8020080

Reitman, S., Frankel, S., (1957).A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminases. American Journal of Clinical Pathology,28 (1), 56 - 63.doi.org/10.1093/ajcp/28.1.56

Selvaraj. V., Tomblin, J., Yeager-Armistead M., Murray, E., 2013. Selenium (sodium selenite) causes cytotoxicity and apoptotic mediated cell death in PLHC-1fish cell line through DNA and mitochondrial membrane potential damage. Ecotoxicology and Environmental Safety 87, 80–8. doi: 10.1016/j.ecoenv.2012.09.028

Selvaraj, V., Yeager‐Armstead, M., Murray, E., 2012. Protective and antioxidant role of selenium on arsenic trioxide-induced oxidative stress and genotoxicity in the fish hepatoma cell line PLHC‐1. Environmental Toxicology and Chemistry, 31(12), 2861-9. doi: 10.1002/etc.2022

Sharabi, K., Tavares, C.D., Rines, A.K., Puigserver, P., 2015.Molecular pathophysiology of hepatic glucose production. Molecular Aspects of Medicine, 46, 21–33. doi:10.1016/j.mam.2015.09.003

Singh, M., Tiwary S, Patil D, Sharma D, Shukla V (2006). Gamma-GlutamylTranspeptidase (GGT) As A Marker In Obstructive Jaundice. The Internet Journal of Surgery, 9 (2), 1 - 4

Soetan, K.O., Olaiya, C.O., Oyewole, O.E., 2010. The importance of mineral elements for humans, domestic animals and plants: A review. African Journal of Food Science, 4 (5), 200-222.

Steinbrenner, H., Speckmann, B., Pinto, A., Sies, H., 2011. High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism. Journal of Clinical Biochemistry and Nutrition, 48 (1), 40–45. doi: 10.3164/jcbn.11-002FR

Steinbrenner H. Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radic Biol Med. 2013, 65:1538-1547. doi: 10.1016/j.freeradbiomed.2013.07.016.

Stranges, S., Marshall, J.R., Natarajan, R., Donahue, R.P., Trevisan, M., Combs, G.F., Cappuccio, F.P., Ceriello, A., Reid, M.E.,2007. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial.Annals of Internal Medicine 147, 217–223.

Szasz, G., 1974. Gamma-Glutamyltranspeptidase. In: Bergmeyer HU. Methoden der enzymatischenAnalyse.Weinheim: VerlagChemie, p. 757.

Tack, C., Pohlmeier, H., Behnke, T., Schmid, V., Grenningloh, M., Forst, T., Pfützner, A., 2012. Accuracy Evaluation of Five Blood Glucose Monitoring Systems Obtained from the Pharmacy: A European Multicenter Study with 453 Subjects. Diabetes Technology and Therapeutics, 14 (4), 330–337. http://doi.org/10.1089/dia.2011.0170

Thapa, B.R., Anuj, W., 2007. Liver Function Tests and their Interpretation. Indian Journal of Pediatrics, 74, 663–671.

Vinceti M, Filippini T, Rothman KJ. Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Epidemiol. 2018, 33 (9):789-810. doi: 10.1007/s10654-018-0422-8

Wu, H., Deng, X., Shi, Y., Su, Y., Wei, J., Duan, H., 2016. PGC-1α, glucose metabolism and type 2 diabetes mellitus.Journal of Endocrinology, 229, R99–R115.doi: 10.1530/JOE-16-0021

Wu, H., Kanatous, S.B., Thurmond, F.A., Gallardo, T., Isotani, E., Bassel-Duby, R., Williams, R.S.,2002. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.Science, 296 (5566), 349–52.

Zhou J, Huang K, Lei XG. Selenium and diabetes—evidence from animal studies. Free Radic Biol Med 2013;65:1548–56.

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