Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice

  • Choi, Sung-In (Department of Food Science and Nutrition, Pusan National University) ;
  • Lee, Hyun-Ah (Department of Food Science and Nutrition, Pusan National University) ;
  • Han, Ji-Sook (Department of Food Science and Nutrition, Pusan National University)
  • Received : 2016.02.15
  • Accepted : 2016.05.10
  • Published : 2016.10.01
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Abstract

BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

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References

  1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:4-14. https://doi.org/10.1016/j.diabres.2009.10.007
  2. Bell DS, O'Keefe JH, Jellinger P. Postprandial dysmetabolism: the missing link between diabetes and cardiovascular events? Endocr Pract 2008;14:112-24. https://doi.org/10.4158/EP.14.1.112
  3. Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999;48:937-42. https://doi.org/10.2337/diabetes.48.5.937
  4. Zheng J, Woo SL, Hu X, Botchlett R, Chen L, Huo Y, Wu C. Metformin and metabolic diseases: a focus on hepatic aspects. Front Med 2015;9:173-86. https://doi.org/10.1007/s11684-015-0384-0
  5. Derosa G, Maffioli P. ${\alpha}$-Glucosidase inhibitors and their use in clinical practice. Arch Med Sci 2012;8:899-906.
  6. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360-72. https://doi.org/10.1001/jama.287.3.360
  7. Baus D, Heermeier K, De Hoop M, Metz-Weidmann C, Gassenhuber J, Dittrich W, Welte S, Tennagels N. Identification of a novel AS160 splice variant that regulates GLUT4 translocation and glucoseuptake in rat muscle cells. Cell Signal 2008;20:2237-46. https://doi.org/10.1016/j.cellsig.2008.08.010
  8. Treebak JT, Glund S, Deshmukh A, Klein DK, Long YC, Jensen TE, Jorgensen SB, Viollet B, Andersson L, Neumann D, Wallimann T, Richter EA, Chibalin AV, Zierath JR, Wojtaszewski JF. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes 2006;55:2051-8. https://doi.org/10.2337/db06-0175
  9. Hajiaghaalipour F, Khalilpourfarshbafi M, Arya A. Modulation of glucose transporter protein by dietary flavonoids in type 2 diabetes mellitus. Int J Biol Sci 2015;11:508-24. https://doi.org/10.7150/ijbs.11241
  10. Jung UJ, Lee MK, Jeong KS, Choi MS. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucoseregulating enzymes in C57BL/KsJ-db/db mice. J Nutr 2004;134: 2499-503. https://doi.org/10.1093/jn/134.10.2499
  11. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001;414:799-806. https://doi.org/10.1038/414799a
  12. Perry LM , Metzger J. Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses. Cambridge (MA): MIT Press; 1980.
  13. Kim MJ, Lee HJ, Wiryowidagdo S, Kim HK. Antihypertensive effects of Gynura procumbens extract in spontaneously hypertensive rats. J Med Food 2006;9:587-90. https://doi.org/10.1089/jmf.2006.9.587
  14. Akowuah GA, Mariam A, Chin JH. The effect of extraction temperature on total phenols and antioxidant activity of Gynura procumbens leaf. Pharmacogn Mag 2009;17:81-5.
  15. Iskander MN, Song Y, Coupar IM, Jiratchariyakul W. Antiinflammatory screening of the medicinal plant Gynura procumbens. Plant Foods Hum Nutr 2002;57:233-44. https://doi.org/10.1023/A:1021851230890
  16. Kaewseejan N, Puangpronpitag D, Nakornriab M. Evaluation of phytochemical composition and antibacterial property of Gynura procumbens extract. Asian J Plant Sci 2012;11:77-82. https://doi.org/10.3923/ajps.2012.77.82
  17. Lee HW, Hakim P, Rabu A, Sani HA. Antidiabetic effect of Gynura procumbens leaves extracts involve modulation of hepatic carbohydrate metabolism in streptozotocin-induced diabetic rats. J Med Plants Res 2012;6:796-812.
  18. Algariri K, Meng KY, Atangwho IJ, Asmawi MZ, Sadikun A, Murugaiyah V, Ismail N. Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts. Asian Pac J Trop Biomed 2013;3:358-66. https://doi.org/10.1016/S2221-1691(13)60077-5
  19. Kaewseejan N, Sutthikhum V, Siriamornpun S. Potential of Gynura procumbens leaves as source of flavonoid-enriched fractions with enhanced antioxidant capacity. J Funct Foods 2015;12:120-8. https://doi.org/10.1016/j.jff.2014.11.001
  20. Seifter S, Dayton S. The estimation of glycogen with the anthrone reagent. Arch Biochem 1950;25:191-200.
  21. Baron AD, Zhu JS, Zhu JH, Weldon H, Maianu L, Garvey WT. Glucosamine induces insulin rsistance in vivo by affecting GLUT 4 translocation in skeletal muscle. J Clin Invest 1995;96:2792-801. https://doi.org/10.1172/JCI118349
  22. Klip A, Ramlal T, Young DA, Holloszy JO. Insulin-induced translocation of glucose transporters in rat hindlimb muscles. FEBS Lett 1987;224:224-30. https://doi.org/10.1016/0014-5793(87)80452-0
  23. Klip A, Pâquet MR. Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care 1990;13:228-43. https://doi.org/10.2337/diacare.13.3.228
  24. Goyal A, Singh S, Tandon N, Gupta N, Gupta YK. Effect of atorvastatin on pancreatic Beta-cell function and insulin resistance in type 2 diabetes mellitus patients: a randomized pilot study. Can J Diabetes 2014;38:466-72. https://doi.org/10.1016/j.jcjd.2014.01.006
  25. Fonseca V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 2003;115 Suppl 8A:42S-48S. https://doi.org/10.1016/j.amjmed.2003.09.005
  26. Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 1988;37:1549-58. https://doi.org/10.2337/diab.37.11.1549
  27. Chou W, Chung MH, Wang HY, Chen JH, Chen WL, Guo HR, Lin HJ, Su SB, Huang CC, Hsu CC. Clinical characteristics of hyperglycemic crises in patients without a history of diabetes. J Diabetes Investig 2014;5:657-62. https://doi.org/10.1111/jdi.12209
  28. Zephy D, Ahmad J. Type 2 diabetes mellitus: role of melatonin and oxidative stress. Diabetes Metab Syndr 2015;9:127-31. https://doi.org/10.1016/j.dsx.2014.09.018
  29. Goldstein DE, Peth SB, England JD, Hess RL, Da Costa J. Effects of acute changes in blood glucose on HbA1c. Diabetes 1980;29:623-8. https://doi.org/10.2337/diab.29.8.623
  30. Twomey PJ, Viljoen A, Reynolds TM, Wierzbicki AS. Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes. Diabetes Care 2004;27:2569-70.
  31. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 2003;135C:357-64.
  32. Alkhalidy H, Moore W, Zhang Y, McMillan R, Wang A, Ali M, Suh KS, Zhen W, Cheng Z, Jia Z, Hulver M, Liu D. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic ${\beta}$-cell mass in middle-aged obese diabetic mice. J Diabetes Res 2015;2015:532984.
  33. Orland MJ, Permutt MA. Quantitative analysis of pancreatic proinsulin mRNA in genetically diabetic (db/db) mice. Diabetes 1987;36:341-7. https://doi.org/10.2337/diab.36.3.341
  34. Kannel WB, Wilson PW, Zhang TJ. The epidemiology of impaired glucose tolerance and hypertension. Am Heart J 1991;121:1268-73. https://doi.org/10.1016/0002-8703(91)90432-H
  35. Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio heart study. Diabetes Care 1997;20:1087-92. https://doi.org/10.2337/diacare.20.7.1087
  36. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402-10. https://doi.org/10.1210/jcem.85.7.6661
  37. Dohm GL. Invited review: Regulation of skeletal muscle GLUT-4 expression by exercise. J Appl Physiol (1985) 2002;93:782-7. https://doi.org/10.1152/japplphysiol.01266.2001
  38. Ojuka EO, Goyaram V, Smith JA. The role of CaMKII in regulating GLUT4 expression in skeletal muscle. Am J Physiol Endocrinol Metab 2012;303:E322-31. https://doi.org/10.1152/ajpendo.00091.2012
  39. Hardie DG. Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. FEBS Lett 2008;582:81-9. https://doi.org/10.1016/j.febslet.2007.11.018
  40. Larance M, Ramm G, Stockli J, van Dam EM, Winata S, Wasinger V, Simpson F, Graham M, Junutula JR, Guilhaus M, James DE. Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking. J Biol Chem 2005;280:37803-13. https://doi.org/10.1074/jbc.M503897200
  41. Eid HM, Martineau LC, Saleem A, Muhammad A, Vallerand D, Benhaddou-Andaloussi A, Nistor L, Afshar A, Arnason JT, Haddad PS. Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res 2010;54:991-1003. https://doi.org/10.1002/mnfr.200900218
  42. Wu C, Zhang X, Zhang X, Luan H, Sun G, Sun X, Wang X, Guo P, Xu X. The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice. J Nutr Biochem 2014;25:412-9. https://doi.org/10.1016/j.jnutbio.2013.12.002
  43. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, Hue L, Andreelli F. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 2006;574:41-53. https://doi.org/10.1113/jphysiol.2006.108506
  44. Takikawa M, Inoue S, Horio F, Tsuda T. Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J Nutr 2010;140:527-33. https://doi.org/10.3945/jn.109.118216
  45. Hijmans BS, Grefhorst A, Oosterveer MH, Groen AK. Zonation of glucose and fatty acid metabolism in the liver: mechanism and metabolic consequences. Biochimie 2014;96:121-9. https://doi.org/10.1016/j.biochi.2013.06.007
  46. Baik SH. The genes of hepatic glucose metabolism and insulin signaling. J Korean Diabetes Assoc 1999;23:1-6.
  47. Ahn J, Um MY, Lee H, Jung CH, Heo SH, Ha TY. Eleutheroside E, an active component of Eleutherococcus senticosus, ameliorates insulin resistance in type 2 diabetic db/db mice. Evid Based Complement Alternat Med 2013;2013:934183.
  48. Yarushkin AA, Kachaylo EM, Pustylnyak VO. The constitutive androstane receptor activator 4-[(4R,6R)-4,6-diphenyl-1,3-dioxan-2-yl]-N,N-dimethylaniline inhibits the gluconeogenic genes PEPCK and G6Pase through the suppression of HNF4alpha and FOXO1 transcriptional activity. Br J Pharmacol 2013;168:1923-32. https://doi.org/10.1111/bph.12090
  49. Eid HM, Nachar A, Thong F, Sweeney G, Haddad PS. The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag 2015;11:74-81. https://doi.org/10.4103/0973-1296.149708

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