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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 303902, 12 pages
http://dx.doi.org/10.1155/2013/303902
Research Article

Quercetin Preserves β-Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China

Received 22 December 2012; Revised 26 January 2013; Accepted 26 January 2013

Academic Editor: Ravirajsinh N. Jadeja

Copyright © 2013 Jian-Mei Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Nakagawa, H. Hu, S. Zharikov et al., “A causal role for uric acid in fructose-induced metabolic syndrome,” The American Journal of Physiology, vol. 290, no. 3, pp. F625–F631, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. R. J. Johnson, M. S. Segal, Y. Sautin et al., “Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease,” The American Journal of Clinical Nutrition, vol. 86, no. 4, pp. 899–906, 2007. View at Scopus
  3. J. P. Bantle, “Dietary fructose and metabolic syndrome and diabetes,” Journal of Nutrition, vol. 139, no. 6, pp. 1263S–1268S, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. M. J. Dekker, Q. Su, C. Baker, A. C. Rutledge, and K. Adeli, “Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome,” The American Journal of Physiology, vol. 299, no. 5, pp. E685–E694, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. G. A. Kyriazis, M. M. Soundarapandian, and B. Tyrberg, “Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 8, pp. E524–E532, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Seufert, T. J. Kieffer, and J. F. Habener, “Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 2, pp. 674–679, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. T. Morioka, E. Asilmaz, J. Hu et al., “Disruption of leptin receptor expression in the pancreas directly affects β cell growth and function in mice,” Journal of Clinical Investigation, vol. 117, no. 10, pp. 2860–2868, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Kitamura, J. Nakae, Y. Kitamura et al., “The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth,” Journal of Clinical Investigation, vol. 110, no. 12, pp. 1839–1847, 2002. View at Publisher · View at Google Scholar · View at Scopus
  9. E. Bernal-Mizrachi, W. Wen, S. Stahlhut, C. M. Welling, and M. A. Permutt, “Islet β cell expression of constitutively active Akt1/PKBα induces striking hypertrophy, hyperplasia, and hyperinsulinemia,” Journal of Clinical Investigation, vol. 108, no. 11, pp. 1631–1638, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. R. L. Tuttle, N. S. Gill, W. Pugh et al., “Regulation of pancreatic β-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα,” Nature Medicine, vol. 7, no. 10, pp. 1133–1137, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. T. L. Jetton, J. Lausier, K. LaRock et al., “Mechanisms of compensatory β-cell growth in insulin-resistant rats: roles of Akt kinase,” Diabetes, vol. 54, no. 8, pp. 2294–2304, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. Buteau and D. Accili, “Regulation of pancreatic β-cell function by the forkhead protein FoxO1,” Diabetes, Obesity and Metabolism, vol. 9, no. 2, pp. 140–146, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Nakae, W. H. Biggs III, T. Kitamura et al., “Regulation of insulin action and pancreatic β-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1,” Nature Genetics, vol. 32, no. 2, pp. 245–253, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Okamoto, M. L. Hribal, H. V. Lin, W. R. Bennett, A. Ward, and D. Accili, “Role of the forkhead protein FoxO1 in β cell compensation to insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 3, pp. 775–782, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. J. M. Li, Y. C. Li, L. D. Kong, and Q. H. Hu, “Curcumin inhibits hepatic proteintyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats,” Hepatology, vol. 51, no. 5, pp. 1555–1566, 2010. View at Publisher · View at Google Scholar
  16. L. Vilà, N. Roglans, M. Alegret, R. M. Sánchez, M. Vázquez-Carrera, and J. C. Laguna, “Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (Ser/Thr) phosphoproteins involved in leptin transduction mediate the effect of Fructose on rat liver lipid metabolism,” Hepatology, vol. 48, no. 5, pp. 1506–1516, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. S. J. Haring and R. B. S. Harris, “The relation between dietary fructose, dietary fat and leptin responsiveness in rats,” Physiology and Behavior, vol. 104, no. 5, pp. 914–922, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Qu, D. Su, J. Altomonte et al., “PPARα mediates the hypolipidemic action of fibrates by antagonizing FoxO1,” The American Journal of Physiology, vol. 292, no. 2, pp. E421–E434, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. L. H. Yao, Y. M. Jiang, J. Shi et al., “Flavonoids in food and their health benefits,” Plant Foods for Human Nutrition, vol. 59, no. 3, pp. 113–122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Muthian and J. J. Bright, “Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte,” Journal of Clinical Immunology, vol. 24, no. 5, pp. 542–552, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. S. C. Bischoff, “Quercetin: potentials in the prevention and therapy of disease,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 11, no. 6, pp. 733–740, 2008. View at Publisher · View at Google Scholar
  22. M. Kobori, S. Masumoto, Y. Akimoto, and H. Oike, “Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice,” Molecular Nutrition and Food Research, vol. 55, no. 4, pp. 530–540, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. S. K. Panchal, H. Poudyal, and L. Brown, “Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats,” Journal of Nutrition, vol. 142, no. 6, pp. 1026–1032, 2012. View at Publisher · View at Google Scholar
  24. O. Coskun, M. Kanter, A. Korkmaz, and S. Oter, “Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas,” Pharmacological Research, vol. 51, no. 2, pp. 117–123, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. S. M. Jeong, M. J. Kang, H. N. Choi, J. H. Kim, and J. I. Kim, “Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice,” Nutrition Research and Practice, vol. 6, no. 3, pp. 201–207, 2012. View at Publisher · View at Google Scholar
  26. J. H. Kim, M. J. Kang, H. N. Choi, S. M. Jeong, Y. M. Lee, and J. Kim, “Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus,” Nutrition Research and Practice, vol. 5, no. 2, pp. 107–111, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. Q. H. Hu, C. Wang, J. M. Li, D. M. Zhang, and L. D. Kong, “Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement,” The American Journal of Physiology, vol. 297, no. 4, pp. F1080–F1091, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. U. J. Jung, M. K. Lee, Y. B. Park, M. A. Kang, and M. S. Choi, “Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice,” International Journal of Biochemistry and Cell Biology, vol. 38, no. 7, pp. 1134–1145, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Kitamura, Y. Kido, S. Nef, J. Merenmies, L. F. Parada, and D. Accili, “Preserved pancreatic β-cell development and function in mice lacking the insulin receptor-related receptor,” Molecular and Cellular Biology, vol. 21, no. 16, pp. 5624–5630, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. J. A. Moibi, D. Gupta, T. L. Jetton, M. Peshavaria, R. Desai, and J. L. Leahy, “Peroxisome proliferator-activated receptor-γ regulates expression of PDX-1 and NKX6.1 in INS-1 cells,” Diabetes, vol. 56, no. 1, pp. 88–95, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. R. N. Kulkarni, J. C. Brüning, J. N. Winnay, C. Postic, M. A. Magnuson, and R. Kahn, “Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes,” Cell, vol. 96, no. 3, pp. 329–339, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. G. Meur, Q. Qian, G. da Silva Xavier et al., “Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic β cells (MIN6),” The Journal of Biological Chemistry, vol. 286, no. 15, pp. 13647–13656, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. K. L. Stanhope, J. M. Schwarz, N. L. Keim et al., “Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans,” Journal of Clinical Investigation, vol. 119, no. 5, pp. 1322–1334, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. R. J. Johnson, S. E. Perez-Pozo, Y. Y. Sautin et al., “Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes?” Endocrine Reviews, vol. 30, no. 1, pp. 96–116, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. O. Kluth, F. Mirhashemi, S. Scherneck et al., “Dissociation of lipotoxicity and glucotoxicity in a mouse model of obesity associated diabetes: role of forkhead box O1 (FOXO1) in glucose-induced beta cell failure,” Diabetologia, vol. 54, no. 3, pp. 605–616, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. E. K. Kim, K. B. Kwon, M. Y. Song et al., “Flavonoids protect against cytokine-induced pancreatic β-cell damage through suppression of nuclear factor κB activation,” Pancreas, vol. 35, no. 4, pp. e1–e9, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. C. Y. Lin, C. C. Ni, M. C. Yin, and C. K. Lii, “Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway,” Cytokine, vol. 59, no. 1, pp. 65–71, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. X. Dai, Y. Ding, Z. Zhang, X. Cai, and Y. Li, “Quercetin and quercitrin protect against cytokineinduced injuries in RINm5F β-cells via the mitochondrial pathway and NF-κB signaling,” International Journal of Molecular Medicine, vol. 31, no. 1, pp. 265–271, 2013.
  39. A. S. Dias, M. Porawski, M. Alonso, N. Marroni, P. S. Collado, and J. González-Gallego, “Quercetin decreases oxidative stress, NF-κB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats,” Journal of Nutrition, vol. 135, no. 10, pp. 2299–2304, 2005. View at Scopus
  40. M. Vessal, M. Hemmati, and M. Vasei, “Antidiabetic effects of quercetin in streptozocin-induced diabetic rats,” Comparative Biochemistry and Physiology C, vol. 135, no. 3, pp. 357–364, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. S. C. Martinez, C. Cras-Méneur, E. Bernal-Mizrachi, and M. A. Permutt, “Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet β-cell,” Diabetes, vol. 55, no. 6, pp. 1581–1591, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. T. J. Kieffer and J. F. Habener, “The adipoinsular axis: effects of leptin on pancreatic β-cells,” The American Journal of Physiology, vol. 278, no. 1, pp. E1–E14, 2000. View at Scopus
  43. R. N. Kulkarni, Z. L. Wang, R. M. Wang et al., “Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice,” Journal of Clinical Investigation, vol. 100, no. 11, pp. 2729–2736, 1997. View at Scopus
  44. T. Uchida, T. Nakamura, N. Hashimoto et al., “Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice,” Nature Medicine, vol. 11, no. 2, pp. 175–182, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Kitamura, Y. I. Feng, Y. I. Kitamura et al., “Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake,” Nature Medicine, vol. 12, no. 5, pp. 534–540, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. G. Yang, C. Y. Lim, C. Li et al., “FoxO1 inhibits leptin regulation of pro-opiomelanocortin promoter activity by blocking STAT3 interaction with specificity protein 1,” The Journal of Biological Chemistry, vol. 284, no. 6, pp. 3719–3727, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. J. S. Choi, S. W. Kang, J. Li et al., “Blockade of oxidized LDL-triggered endothelial apoptosis by quercetin and rutin through differential signaling pathways involving JAK2,” Journal of Agricultural and Food Chemistry, vol. 57, no. 5, pp. 2079–2086, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Manu, C. Ionescu-Tirgoviste, J. Tsang, B. A. Napolitano, M. L. Lesser, and C. U. Correll, “Dysmetabolic signals in, “metabolically healthy” obesity,” Obesity Research and Clinical Practice, vol. 6, no. 1, pp. e9–e20, 2012. View at Publisher · View at Google Scholar
  49. A. A. Qureshi, D. A. Khan, W. Mahjabeen, C. J. Papasian, and N. Qureshi, “Suppression of nitric oxide production and cardiovascular risk factors in healthy seniors and hypercholesterolemic subjects by a combination of polyphenols and vitamins,” Journal of Clinical and Experimental Cardiology, vol. S5, article 8, 2012.
  50. G. Williamson and A. Carughi, “Polyphenol content and health benefits of raisins,” Nutrition Research, vol. 30, no. 8, pp. 511–519, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Leiherer, A. Mundlein, and H. Drexel, “Phytochemicals and their impact on adipose tissue inflammation and diabetes,” Vascular Pharmacology, vol. 58, no. 1-2, pp. 3–20, 2013. View at Publisher · View at Google Scholar