Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes

  • Authors:
    • Shan‑Bo Ma
    • Rui Zhang
    • Shan Miao
    • Bin Gao
    • Yang Lu
    • Sen Hui
    • Long Li
    • Xiao‑Peng Shi
    • Ai‑Dong Wen
  • View Affiliations

  • Published online on: April 7, 2017     https://doi.org/10.3892/mmr.2017.6450
  • Pages: 3803-3809
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Abstract

Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG. Cellular glycogen content was determined using a glycogen assay kit. Reactive oxygen species (ROS) production was determined using dihydroethidium staining and flow cytometry. c‑JUN N‑terminal kinase (JNK)/insulin receptor substrate 1 (IRS1)/AKT/GSK signaling was explored using western blot analysis in HepG2 cells treated with high glucose and/or EGCG or N-acetyl-cysteine. High glucose significantly decreased the levels of phosphorylated AKT and GSK in HepG2 cells and mouse primary hepatocytes. Pretreatment with EGCG significantly restored the activation of AKT and GSK in HepG2 cells and primary hepatocytes exposed to high glucose. In HepG2 cells and primary hepatocytes, glycogen synthesis was improved by EGCG treatment in a dose‑dependent manner. High glucose significantly stimulated the production of ROS while EGCG protected high glucose‑induced ROS production. ROS is known to serve a major role in high glucose induced‑insulin resistance by increasing JNK and IRS1 serine phosphorylation. In the present study, EGCG was observed to enhance the insulin‑signaling pathway. EGCG ameliorated high glucose‑induced insulin resistance in the hepatocytes by potentially decreasing ROS‑induced JNK/IRS1/AKT/GSK signaling.

References

1 

Ezenwaka CE, Okoye O, Esonwune C, Onuoha P, Dioka C, Osuji C, Oguejiofor C and Meludu S: High prevalence of abdominal obesity increases the risk of the metabolic syndrome in Nigerian type 2 diabetes patients: Using the International diabetes federation worldwide definition. Metab Syndr Relat Disord. 12:277–282. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Cable JC, Tan GD, Alexander SP and O'Sullivan SE: The effects of obesity, diabetes and metabolic syndrome on the hydrolytic enzymes of the endocannabinoid system in animal and human adipocytes. Lipids Health Dis. 13:432014. View Article : Google Scholar : PubMed/NCBI

3 

Liu CY, Huang CJ, Huang LH, Chen IJ, Chiu JP and Hsu CH: Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: A randomized, double-blinded, and placebo-controlled trial. PLoS One. 9:e911632014. View Article : Google Scholar : PubMed/NCBI

4 

Gilbert RE: The endothelium in diabetic nephropathy. Curr Atheroscler Rep. 16:4102014. View Article : Google Scholar : PubMed/NCBI

5 

Crespy V and Williamson G: A review of the health effects of green tea catechins in in vivo animal models. J Nutr. 134 Suppl 12:S3431–S3440. 2004.

6 

Basu A, Sanchez K, Leyva MJ, Wu M, Betts NM, Aston CE and Lyons TJ: Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J Am Coll Nutr. 29:31–40. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Sae-Tan S, Grove KA and Lambert JD: Weight control and prevention of metabolic syndrome by green tea. Pharmacol Res. 64:146–154. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Ihm SH, Jang SW, Kim OR, Chang K, Oak MH, Lee JO, Lim DY and Kim JH: Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome. Atherosclerosis. 224:377–383. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Sae-Tan S, Rogers CJ and Lambert JD: Voluntary exercise and green tea enhance the expression of genes related to energy utilization and attenuate metabolic syndrome in high fat fed mice. Mol Nutr Food Res. 58:1156–1159. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Thielecke F and Boschmann M: The potential role of green tea catechins in the prevention of the metabolic syndrome-A review. Phytochemistry. 70:11–24. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Senger AE Vieira, Schwanke CH, Gomes I and Gottlieb MG Valle: Effect of green tea (Camellia sinensis) consumption on the components of metabolic syndrome in elderly. J Nutr Health Aging. 16:738–742. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Cia D, Vergnaud-Gauduchon J, Jacquemot N and Doly M: Epigallocatechin gallate (EGCG) prevents H2O2-induced oxidative stress in primary rat retinal pigment epithelial cells. Curr Eye Res. 39:944–952. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Yang EJ, Lee J, Lee SY, Kim EK, Moon YM, Jung YO, Park SH and Cho ML: EGCG attenuates autoimmune arthritis by inhibition of STAT3 and HIF-1α with Th17/Treg control. PLoS One. 9:e860622014. View Article : Google Scholar : PubMed/NCBI

14 

Zhou J, Farah BL, Sinha RA, Wu Y, Singh BK, Bay BH, Yang CS and Yen PM: Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance. PLoS One. 9:e871612014. View Article : Google Scholar : PubMed/NCBI

15 

Benelli R, Venè R, Bisacchi D, Garbisa S and Albini A: Anti-invasive effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), a natural inhibitor of metallo and serine proteases. Biol Chem. 383:101–105. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Zhao C, She T, Wang L, Su Y, Qu L, Gao Y, Xu S, Cai S and Shou C: Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner. Life Sci. 137:37–43. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Saltiel AR: Insulin signaling in the control of glucose and lipid homeostasis. Handb Exp Pharmacol. 233:51–71. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Hendriksen PH, Oey PL, Wieneke GH, Bravenboer B and Banga JD: Subclinical diabetic neuropathy: Similarities between electrophysiological results of patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 35:690–695. 1992. View Article : Google Scholar : PubMed/NCBI

19 

Eddouks M, Maghrani M and Michel JB: Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats. J Ethnopharmacol. 102:228–232. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Stefano GB, Challenger S and Kream RM: Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. Eur J Nutr. 55:2339–2345. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Bukhari SA, Naqvi SA, Nagra SA, Anjum F, Javed S and Farooq M: Assessing of oxidative stress related parameters in diabetes mellitus type 2: Cause excessive damaging to DNA and enhanced homocysteine in diabetic patients. Pak J Pharm Sci. 28:483–491. 2015.PubMed/NCBI

22 

Tsuneki H, Ishizuka M, Terasawa M, Wu JB, Sasaoka T and Kimura I: Effect of green tea on blood glucose levels and serum proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans. BMC Pharmacol. 4:182004. View Article : Google Scholar : PubMed/NCBI

23 

Hirsch N, Konstantinov A, Anavi S, Aronis A, Hagay Z, Madar Z and Tirosh O: Prolonged feeding with green tea polyphenols exacerbates cholesterol-induced fatty liver disease in mice. Mol Nutr Food Res. 60:2542–2553. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Weisburger JH and Chung FL: Mechanisms of chronic disease causation by nutritional factors and tobacco products and their prevention by tea polyphenols. Food Chem Toxicol. 40:1145–1154. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Raederstorff DG, Schlachter MF, Elste V and Weber P: Effect of EGCG on lipid absorption and plasma lipid levels in rats. J Nutr Biochem. 14:326–332. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Rösen P, Nawroth PP, King G, Moller W, Tritschler HJ and Packer L: The role of oxidative stress in the onset and progression of diabetes and its complications: A summary of a congress series sponsored by UNESCO-MCBN, the American diabetes association and the German diabetes society. Diabetes Metab Res Rev. 17:189–212. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Nishikawa T, Edelstein D and Brownlee M: The missing link: A single unifying mechanism for diabetic complications. Kidney Int Suppl. 77:S26–S30. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Paolisso G and Giugliano D: Oxidative stress and insulin action: Is there a relationship? Diabetologia. 39:357–363. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Rudich A, Kozlovsky N, Potashnik R and Bashan N: Oxidant stress reduces insulin responsiveness in 3T3-L1 adipocytes. Am J Physiol. 272:E935–E940. 1997.PubMed/NCBI

30 

Kyriakis JM and Avruch J: Sounding the alarm: Protein kinase cascades activated by stress and inflammation. J Biol Chem. 271:24313–24316. 1996. View Article : Google Scholar : PubMed/NCBI

31 

Blair AS, Hajduch E, Litherland GJ and Hundal HS: Regulation of glucose transport and glycogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinase signaling pathways. J Biol Chem. 274:36293–36299. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Birnbaum MJ: Turning down insulin signaling. J Clin Invest. 108:655–659. 2001. View Article : Google Scholar : PubMed/NCBI

33 

Liu K, Zhao W, Gao X, Huang F, Kou J and Liu B: Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKKβ and IRS-1 pathways. Atherosclerosis. 223:350–358. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Katakam AK, Chipitsyna G, Gong Q, Vancha AR, Gabbeta J and Arafat HA: Streptozotocin (STZ) mediates acute upregulation of serum and pancreatic osteopontin (OPN): A novel islet-protective effect of OPN through inhibition of STZ-induced nitric oxide production. J Endocrinol. 187:237–247. 2005. View Article : Google Scholar : PubMed/NCBI

35 

Chu J, Zhang H, Huang X, Lin Y, Shen T, Chen B, Man Y, Wang S and Li J: Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. PLoS One. 8:e572312013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
APA
Ma, S., Zhang, R., Miao, S., Gao, B., Lu, Y., Hui, S. ... Wen, A. (2017). Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes. Molecular Medicine Reports, 15, 3803-3809. https://doi.org/10.3892/mmr.2017.6450
MLA
Ma, S., Zhang, R., Miao, S., Gao, B., Lu, Y., Hui, S., Li, L., Shi, X., Wen, A."Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes". Molecular Medicine Reports 15.6 (2017): 3803-3809.
Chicago
Ma, S., Zhang, R., Miao, S., Gao, B., Lu, Y., Hui, S., Li, L., Shi, X., Wen, A."Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes". Molecular Medicine Reports 15, no. 6 (2017): 3803-3809. https://doi.org/10.3892/mmr.2017.6450