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ᴅ-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro

  • Kim, Eunju (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Yoo-Sun (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Kyung-Mi (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Jung, Sangwon (R&D center, TS Corporation) ;
  • Yoo, Sang-Ho (Department of Food Science & Technology, BK21 Plus Team, and Carbohydrate Bioproduct Research Center, Sejong University) ;
  • Kim, Yuri (Department of Nutritional Science and Food Management, Ewha Womans University)
  • 투고 : 2015.02.11
  • 심사 : 2015.05.07
  • 발행 : 2016.02.01

초록

BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. $\small{D}$-xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of $\small{D}$-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with $\small{D}$-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with $\small{D}$-xylose. These groups were maintained for two weeks. The effects of $\small{D}$-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ${\beta}$-cells were analyzed. RESULTS: In vivo, $\small{D}$-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. $\small{D}$-xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of $\small{D}$-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with $\small{D}$-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, $\small{D}$-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, $\small{D}$-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ${\beta}$-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

키워드

참고문헌

  1. Consensus Development Conference on Insulin Resistance. 5-6 November 1997. American Diabetes Association. Diabetes Care 1998;21:310-4.
  2. Li PB, Lin WL, Wang YG, Peng W, Cai XY, Su WW. Antidiabetic activities of oligosaccharides of Ophiopogonis japonicus in experimental type 2 diabetic rats. Int J Biol Macromol 2012;51:749-55. https://doi.org/10.1016/j.ijbiomac.2012.07.007
  3. Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am 2007;91:1063-77, viii. https://doi.org/10.1016/j.mcna.2007.06.012
  4. Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med (Maywood) 2012;237:481-90. https://doi.org/10.1258/ebm.2012.011372
  5. Turk J, Corbett JA, Ramanadham S, Bohrer A, McDaniel ML. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun 1993;197:1458-64. https://doi.org/10.1006/bbrc.1993.2641
  6. Wada R, Yagihashi S. Nitric oxide generation and poly(ADP ribose) polymerase activation precede beta-cell death in rats with a single high-dose injection of streptozotocin. Virchows Arch 2004;444: 375-82. https://doi.org/10.1007/s00428-003-0967-z
  7. Maiese K, Chong ZZ, Hou J, Shang YC. The vitamin nicotinamide: translating nutrition into clinical care. Molecules 2009;14:3446-85. https://doi.org/10.3390/molecules14093446
  8. Uchigata Y, Yamamoto H, Kawamura A, Okamoto H. Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis. J Biol Chem 1982;257:6084-8.
  9. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998;47:224-9. https://doi.org/10.2337/diab.47.2.224
  10. Morral N. Novel targets and therapeutic strategies for type 2 diabetes. Trends Endocrinol Metab 2003;14:169-75. https://doi.org/10.1016/S1043-2760(03)00031-6
  11. McAnuff MA, Omoruyi FO, Morrison EY, Asemota HN. Changes in some liver enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides) or commercial diosgenin. West Indian Med J 2005;54:97-101.
  12. Brenner RR, Rimoldi OJ, Lombardo YB, Gonzalez MS, Bernasconi AM, Chicco A, Basabe JC. Desaturase activities in rat model of insulin resistance induced by a sucrose-rich diet. Lipids 2003;38:733-42. https://doi.org/10.1007/s11745-003-1121-x
  13. Fung TT, Malik V, Rexrode KM, Manson JE, Willett WC, Hu FB. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr 2009;89:1037-42. https://doi.org/10.3945/ajcn.2008.27140
  14. Kafatos A, Codrington CA. Nutrition and diet for healthy lifestyles in Europe: the 'Eurodiet' Project. Public Health Nutr 1999;2:327-8.
  15. Yokozawa T, Kim HY, Cho EJ. Erythritol attenuates the diabetic oxidative stress through modulating glucose metabolism and lipid peroxidation in streptozotocin-induced diabetic rats. J Agric Food Chem 2002;50:5485-9. https://doi.org/10.1021/jf020168z
  16. Bae YJ, Bak YK, Kim B, Kim MS, Lee JH, Sung MK. Coconut-derived D-xylose affects postprandial glucose and insulin responses in healthy individuals. Nutr Res Pract 2011;5:533-9. https://doi.org/10.4162/nrp.2011.5.6.533
  17. Seri K, Sanai K, Matsuo N, Kawakubo K, Xue C, Inoue S. L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals. Metabolism 1996;45:1368-74. https://doi.org/10.1016/S0026-0495(96)90117-1
  18. Gruzman A, Shamni O, Ben Yakir M, Sandovski D, Elgart A, Alpert E, Cohen G, Hoffman A, Katzhendler Y, Cerasi E, Sasson S. Novel D-xylose derivatives stimulate muscle glucose uptake by activating AMP-activated protein kinase alpha. J Med Chem 2008;51:8096-108. https://doi.org/10.1021/jm8008713
  19. Hanson RW, Reshef L. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annu Rev Biochem 1997;66:581-611. https://doi.org/10.1146/annurev.biochem.66.1.581
  20. Weng Y, Yu L, Cui J, Zhu YR, Guo C, Wei G, Duan JL, Yin Y, Guan Y, Wang YH, Yang ZF, Xi MM, Wen AD. Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats. J Ethnopharmacol 2014;152:553-60. https://doi.org/10.1016/j.jep.2014.02.001
  21. Ananda PK, Kumarappan CT, Sunil C, Kalaichelvan VK. Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats. Asian Pac J Trop Biomed 2012;2:31-5.
  22. Park KJ, Jin HS, Park SH, Kim EH, Kim JK. Antihyperglycemia effect of medicinal plants mixture in streptozotocin-induced diabetic rats. J Korean Soc Food Sci Nutr 2008;37:1554-9. https://doi.org/10.3746/jkfn.2008.37.12.1554
  23. Pierre W, Gildas AJ, Ulrich MC, Modeste WN, Benoit NT, Albert K. Hypoglycemic and hypolipidemic effects of Bersama engleriana leaves in nicotinamide/streptozotocin-induced type 2 diabetic rats. BMC Complement Altern Med 2012;12:264. https://doi.org/10.1186/1472-6882-12-S1-P264
  24. Cheon H, Cho JM, Kim S, Baek SH, Lee MK, Kim KW, Yu SW, Solinas G, Kim SS, Lee MS. Role of JNK activation in pancreatic beta-cell death by streptozotocin. Mol Cell Endocrinol 2010;321:131-7. https://doi.org/10.1016/j.mce.2010.02.016
  25. Novelli M, Bonamassa B, Masini M, Funel N, Canistro D, De Tata V, Martano M, Soleti A, Campani D, Paolini M, Masiello P. Persistent correction of hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice by a non-conventional radical scavenger. Naunyn Schmiedebergs Arch Pharmacol 2010;382:127-37. https://doi.org/10.1007/s00210-010-0524-7
  26. Saravanan R, Pari L. Succinic acid monoethyl ester, a novel insulinotropic agent: effect on lipid composition and lipid peroxidation in streptozotocin-nicotin-amide induced type 2 diabetic rats. Mol Cell Biochem 2007;296:165-76. https://doi.org/10.1007/s11010-006-9312-6
  27. Risbud MV, Bhonde RR. Models of pancreatic regeneration in diabetes. Diabetes Res Clin Pract 2002;58:155-65. https://doi.org/10.1016/S0168-8227(02)00103-1
  28. Prasath GS, Pillai SI, Subramanian SP. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur J Pharmacol 2014;740:248-54. https://doi.org/10.1016/j.ejphar.2014.06.065
  29. Kuo YC, Chen IY, Chang SC, Wu SC, Hung TM, Lee PH, Shimotohno K, Chang MF. Hepatitis C virus NS5A protein enhances gluconeogenesis through upregulation of Akt-/JNK-PEPCK signalling pathways. Liver Int 2014;34:1358-68. https://doi.org/10.1111/liv.12389
  30. Pagliassotti MJ, Shahrokhi KA, Moscarello M. Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: doseresponse studies. Am J Physiol 1994;266:R1637-44.
  31. Mosseri R, Waner T, Shefi M, Shafrir E, Meyerovitch J. Gluconeogenesis in non-obese diabetic (NOD) mice: in vivo effects of vandadate treatment on hepatic glucose-6-phoshatase and phosphoenolpyruvate carboxykinase. Metabolism 2000;49:321-5. https://doi.org/10.1016/S0026-0495(00)90132-X
  32. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, Zhao G, Marsh K, Kym P, Jung P, Camp HS, Frevert E. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 2006;3:403-16. https://doi.org/10.1016/j.cmet.2006.05.005
  33. Hardie DG. The AMP-activated protein kinase pathway--new players upstream and downstream. J Cell Sci 2004;117:5479-87. https://doi.org/10.1242/jcs.01540
  34. Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG Jr, Xiong Y, Daniel KW, Floering L, Collins S. p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem 2005;280:42731-7. https://doi.org/10.1074/jbc.M506223200
  35. Qiu J, Maekawa K, Kitamura Y, Miyata Y, Tanaka K, Tanaka T, Soga M, Tsuda T, Matsui T. Stimulation of glucose uptake by theasinensins through the AMP-activated protein kinase pathway in rat skeletal muscle cells. Biochem Pharmacol 2014;87:344-51. https://doi.org/10.1016/j.bcp.2013.10.029
  36. Lee BH, Hsu WH, Liao TH, Pan TM. The Monascus metabolite monascin against TNF-${\alpha}$-induced insulin resistance via suppressing PPAR-${\gamma}$ phosphorylation in C2C12 myotubes. Food Chem Toxicol 2011;49:2609-17. https://doi.org/10.1016/j.fct.2011.07.005
  37. Kim MS, Hur HJ, Kwon DY, Hwang JT. Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol Cell Endocrinol 2012;358:127-34. https://doi.org/10.1016/j.mce.2012.03.013
  38. Gannon MC, Nuttall FQ. Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition. Nutr Metab (Lond) 2006;3:16. https://doi.org/10.1186/1743-7075-3-16
  39. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab 2000;85:2970-3. https://doi.org/10.1210/jcem.85.8.6854

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