Heeyoung Chae; Patrick Gilon

doi:10.4093/dmj.2015.39.1.27

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Editorial Islet Studies and Transplantation Can Tea Extracts Exert a Protective Effect Against Diabetes by Reducing Oxidative Stress and Decreasing Glucotoxicity in Pancreatic β-Cells?: Heeyoung Chae, Patrick Gilon; Diabetes & Metabolism Journal 2015;39(1):27-30.
DOI: https://doi.org/10.4093/dmj.2015.39.1.27
Published online: February 16, 2015

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Pôle d'Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.

Corresponding author: Heeyoung Chae. Pôle d'Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate 55, 1200 Woluwe-Saint-Lambert, Brussels, Belgium. heeyoung.chae@uclouvain.be

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Glucose is the main physiological stimulus of pancreatic β-cells. However, chronic exposure of β-cells to elevated glucose concentrations induces glucotoxicity. In animal models of type 2 diabetes, it has been shown that several days of hyperglycemia impairs glucose-stimulated insulin secretion and increases β-cell apoptosis. In patients with type 2 diabetes, the multiple disorders caused by chronic hyperglycemia in β-cells include elevated basal insulin secretion, increased sensitivity to glucose, diminished response to insulinotropic stimuli and substantial depletion of insulin hoarding [1,2]. These defects associated with insulin resistance lead to a progressive loss of β-cell mass and function and to the onset of diabetes. It is crucial to study the mechanisms by which glucotoxicity induces β-cell failure to develop therapeutic strategies for protecting and recovering a functional β-cell mass. Several mechanisms might explain the glucotoxicity due to prolonged hyperglycemia, such as β-cell exhaustion, oxidative stress induced by free radical oxygen species, endoplasmic reticulum (ER) stress, inflammation caused by proinflammatory cytokines and chemokines, loss of neogenesis, proliferation of β-cells, and so on [3,4,5,6,7,8,9,10]. However, the precise mechanisms of glucotoxicity and its contribution to the pathology of type 2 diabetes mellitus (T2DM) are still not fully understood.

Previous reports have shown that the over-production of reactive oxygen species (ROS), primarily due to hyperglycemia, causes oxidative stress in various tissues. ROS are free radicals that are intermediate metabolites derived from oxygen metabolism in mitochondria. They play an important role in both physiology and pathology in β-cells. ROS are continuously produced by the mitochondrial electron transport system as a byproduct of the oxidative phosphorylation pathway; however, normal cells have antioxidant defenses to rapidly neutralize ROS and maintain an optimal redox potential for appropriate biological cell function [2,11]. This optimal redox balance is impaired in T2DM because of increased ROS production and insufficient endogenous anti-oxidant defenses of the β-cells. Hence, antioxidant therapy could be useful for treating T2DM. Antioxidants are reducing agents, such as thiols, ascorbic acid, or polyphenols, and are widely used in dietary supplements for the prevention of diseases, such as cancer, coronary heart disease, and various inflammatory diseases. Plants and animals have multiple types of antioxidants, such as glutathione, vitamin C, vitamin A, and vitamin E, as well as antioxidant enzymes, such as superoxide dismutase 1 and 2 (SOD1, 2), glutathione peroxidase 1 (GPX1), and catalase (CAT) [12]. Insufficient amounts of antioxidants or antioxidant enzyme activities can cause oxidative stress and damage or ultimately kill cells. Previous studies in β-cell lines, isolated rodent islets, and diabetic animal models have shown that anti-oxidants can protect β-cells against the toxic effects of high glucose concentrations on insulin gene expression, insulin secretion and β-cell survival. Antioxidant (pre)treatment of diabetic animal models has demonstrated several protective effects against diabetic complications, including the gradual improvement of insulin sensitivity and the enhancement of β-cell function and survival [13,14,15,16].

Tea extracts have been widely used for many centuries as a beverage in traditional medicine in Asia for treating various diseases, including urinary lithiasis, edema, eruptive fever, influenza, rheumatism, hepatitis, jaundice, and renal calculus. Tablets or capsules containing dried leaves are also available as dietary supplements. Orthosiphon stamineus (OS) is a popular medicinal plant in Southeast Asia known for its diuretic, uricosuric, antioxidant, hepatoprotective, anti-inflammatory, antidiabetic, and antihypertensive effects and for its protective action against menstrual disorders. Several therapeutic effects of OS have been ascribed to polyphenol, the most abundant compound in the leaf, which has been reported to reduce oxidative stress by inhibiting lipid hyperoxidation [17,18,19,20,21,22,23,24,25].

Previous studies have reported that tea extracts of medicinal plants as an alternative management of T2DM are effective in reducing oxidative stress. Akowuah et al. [26] showed that the free radical-scavenging capabilities of extracts from the dry leaves of OS were comparable to pure synthetic antioxidant butylated hydroxy anisole. Aoshima et al. [27] ascribed the antioxidant effects to polyphenols in the extracts. Syiem and Warjri [28] reported that extracts of Ixeris gracilis exerted antidiabetic and antioxidant effects, which are associated with improved activities of GPX and superoxide dismutase in the liver, kidney, and brain. Kumar et al. [29] showed that the antidiabetic activity of Melastoma malabathricum Linn. leaves is associated with increased levels of SOD, CAT, and GPX.

A portion of the beneficial effects of tea extracts might be explained by their action on the β-cells. Sriplang et al. [30] demonstrated an antidiabetic effect of aqueous extracts of OS and observed a direct stimulatory effect of the extract on insulin secretion from the perfused rat pancreas. Mechanisms other than antioxidant effects of the extracts might contribute to the improved β-cell function. Ortsater et al. [31] reported that green tea catechin exerts profound antidiabetic effects associated with reduced insulin resistance and enhanced pancreatic islet function due to reduction of ER stress. In a paper published on this issue, Lee and his colleagues [32] tested the direct effect of OS extracts on INS-1 cells and evaluated the likelihood that OS extracts could prevent glucotoxicity. They showed that hexane extracts of OS dose-dependently stimulated insulin secretion and insulin and Pdx-1 gene expression and that these effects were associated with an increased level of phosphorylation of phosphoinositide 3-kinase and Akt but not with a change in peroxide levels. Interestingly, the extracts reversed the glucotoxic effects elicited by a 3-day exposure to high glucose levels (30 mM) [32].

According to all of these studies, tea extracts seem to exert multiple beneficial effects for treating diabetes. Several effects are due to the antioxidant action of the extracts, whereas other effects are attributed to a direct action on β-cells involving a stimulation of insulin secretion and a protection against glucotoxicity. Additional studies are, however, required to determine the precise underlying mechanisms. They could help us better understand the therapeutic effects of various tea extracts in the treatment of diabetes.

Acknowledgements

ACKNOWLEDGMENTS

PG is Research Director, and HC is postdoctoral researcher of the Fonds National de la Recherche Scientifique, Brussels.

NOTES

No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Solomon TP, Knudsen SH, Karstoft K, Winding K, Holst JJ, Pedersen BK. Examining the effects of hyperglycemia on pancreatic endocrine function in humans: evidence for in vivo glucotoxicity. J Clin Endocrinol Metab 2012;97:4682-4691. Article PubMed
2. Bensellam M, Laybutt DR, Jonas JC. The molecular mechanisms of pancreatic beta-cell glucotoxicity: recent findings and future research directions. Mol Cell Endocrinol 2012;364:1-27. PubMed
3. Kaiser N, Leibowitz G, Nesher R. Glucotoxicity and beta-cell failure in type 2 diabetes mellitus. J Pediatr Endocrinol Metab 2003;16:5-22. PubMed
4. Pascal SM, Veiga-da-Cunha M, Gilon P, Van Schaftingen E, Jonas JC. Effects of fructosamine-3-kinase deficiency on function and survival of mouse pancreatic islets after prolonged culture in high glucose or ribose concentrations. Am J Physiol Endocrinol Metab 2010;298:E586-E596. Article PubMed
5. Jonas JC, Bensellam M, Duprez J, Elouil H, Guiot Y, Pascal SM. Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes. Diabetes Obes Metab 2009;(Suppl 4):11:65-81. PubMed
6. Khaldi MZ, Guiot Y, Gilon P, Henquin JC, Jonas JC. Increased glucose sensitivity of both triggering and amplifying pathways of insulin secretion in rat islets cultured for 1 wk in high glucose. Am J Physiol Endocrinol Metab 2004;287:E207-E217. Article PubMed
7. Gilon P, Ravier MA, Jonas JC, Henquin JC. Control mechanisms of the oscillations of insulin secretion in vitro and in vivo. Diabetes 2002;51(Suppl 1):S144-S151. Article PubMed PDF
8. Roger B, Papin J, Vacher P, Raoux M, Mulot A, Dubois M, Kerr-Conte J, Voy BH, Pattou F, Charpentier G, Jonas JC, Moustaid-Moussa N, Lang J. Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells. Diabetologia 2011;54:390-402. Article PubMed PDF
9. Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med (Zagreb) 2013;23:266-280. Article PubMed PMC
10. Zhang Z, Li J, Yang L, Chen R, Yang R, Zhang H, Cai D, Chen H. The cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells. J Diabetes Res 2014;2014:712781Article PubMed PMC PDF
11. Roma LP, Duprez J, Takahashi HK, Gilon P, Wiederkehr A, Jonas JC. Dynamic measurements of mitochondrial hydrogen peroxide concentration and glutathione redox state in rat pancreatic beta-cells using ratiometric fluorescent proteins: confounding effects of pH with HyPer but not roGFP1. Biochem J 2012;441:971-978. PubMed
12. Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 2014;1840:2709-2729. Article PubMed
13. Duprez J, Roma LP, Close AF, Jonas JC. Protective antioxidant and antiapoptotic effects of ZnCl2 in rat pancreatic islets cultured in low and high glucose concentrations. PLoS One 2012;7:e46831Article PubMed PMC
14. Kanda Y, Hashiramoto M, Shimoda M, Hamamoto S, Tawaramoto K, Kimura T, Hirukawa H, Nakashima K, Kaku K. Dietary restriction preserves the mass and function of pancreatic beta cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice. J Nutr Biochem 2014 11 15 Epub. DOI: http://dx.doi.org/10.1016/j.jnutbio.2014.10.007.
15. Khaldi MZ, Elouil H, Guiot Y, Henquin JC, Jonas JC. Antioxidants N-acetyl-L-cysteine and manganese(III)tetrakis (4-benzoic acid)porphyrin do not prevent beta-cell dysfunction in rat islets cultured in high glucose for 1 wk. Am J Physiol Endocrinol Metab 2006;291:E137-E146. PubMed
16. Mizukami H, Takahashi K, Inaba W, Tsuboi K, Osonoi S, Yoshida T, Yagihashi S. Involvement of oxidative stress-induced DNA damage, endoplasmic reticulum stress, and autophagy deficits in the decline of beta-cell mass in Japanese type 2 diabetic patients. Diabetes Care 2014;37:1966-1974. PubMed
17. Arafat OM, Tham SY, Sadikun A, Zhari I, Haughton PJ, Asmawi MZ. Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats. J Ethnopharmacol 2008;118:354-360. Article PubMed
18. Yam MF, Lim V, Salman IM, Ameer OZ, Ang LF, Rosidah N, Abdulkarim MF, Abdullah GZ, Basir R, Sadikun A, Asmawi MZ. HPLC and anti-inflammatory studies of the flavonoid rich chloroform extract fraction of Orthosiphon stamineus leaves. Molecules 2010;15:4452-4466. Article PubMed PMC
19. Doleckova I, Rarova L, Gruz J, Vondrusova M, Strnad M, Krystof V. Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves. Fitoterapia 2012;83:1000-1007. Article PubMed
20. Lee YJ, Kim DB, Lee JS, Cho JH, Kim BK, Choi HS, Lee BY, Lee OH. Antioxidant activity and anti-adipogenic effects of wild herbs mainly cultivated in Korea. Molecules 2013;18:12937-12950. Article PubMed PMC
21. Kang SN, Goo YM, Yang MR, Ibrahim RI, Cho JH, Kim IS, Lee OH. Antioxidant and antimicrobial activities of ethanol extract from the stem and leaf of Impatiens balsamina L. (Balsaminaceae) at different harvest times. Molecules 2013;18:6356-6365. Article PubMed PMC
22. Peres RG, Tonin FG, Tavares MF, Rodriguez-Amaya DB. HPLC-DAD-ESI/MS identification and quantification of phenolic compounds in Ilex paraguariensis beverages and on-line evaluation of individual antioxidant activity. Molecules 2013;18:3859-3871. Article PubMed PMC
23. Shivanna N, Naika M, Khanum F, Kaul VK. Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana. J Diabetes Complications 2013;27:103-113. Article PubMed
24. Mohamed EA, Yam MF, Ang LF, Mohamed AJ, Asmawi MZ. Antidiabetic properties and mechanism of action of Orthosiphon stamineus Benth bioactive sub-fraction in streptozotocin-induced diabetic rats. J Acupunct Meridian Stud 2013;6:31-40. Article PubMed
25. Mohamed EA, Mohamed AJ, Asmawi MZ, Sadikun A, Ebrika OS, Yam MF. Antihyperglycemic effect of orthosiphon stamineus benth leaves extract and its bioassay-guided fractions. Molecules 2011;16:3787-3801. Article PubMed PMC
26. Akowuah GA, Ismail Z, Norhayati I, Sadikun A. The effects of different extraction solvents of varying polarities on polyphenols of Orthosiphon stamineus and evaluation of the free radical-scavenging activity. Food Chem 2005;93:311-317.Article
27. Aoshima H, Hirata S, Ayabe S. Antioxidative and anti-hydrogen peroxide activities of various herbal teas. Food Chem 2007;103:617-622.Article
28. Syiem D, Warjri P. Antidiabetic, antioxidant, and TNF-alpha lowering properties of extract of the traditionally used plant Ixeris gracilis in alloxan-induced diabetic mice. Pharm Biol 2015;53:494-502. PubMed
29. Kumar V, Ahmed D, Gupta PS, Anwar F, Mujeeb M. Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of Melastoma malabathricum Linn. leaves in streptozotocin induced diabetic rats. BMC Complement Altern Med 2013;13:222PubMed PMC PDF
30. Sriplang K, Adisakwattana S, Rungsipipat A, Yibchok-Anun S. Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. J Ethnopharmacol 2007;109:510-514. Article PubMed
31. Ortsater H, Grankvist N, Wolfram S, Kuehn N, Sjoholm A. Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice. Nutr Metab (Lond) 2012;9:11Article PubMed PMC PDF
32. Lee HJ, Choi YJ, Park SY, Kim JY, Won KC, Son JK, Kim YW. Hexane extract of Orthosiphon stamineus induces insulin expression and prevents glucotoxicity in INS-1 cells. Diabetes Metab J 2015;39:51-58.Article PubMed PMC

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