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Antihypertensive peptide purified from Styela clava flesh tissue stimulates glucose uptake through AMP-activated protein kinase (AMPK) activation in skeletal muscle cells

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Abstract

Previously, our group described an antihypertensive peptide (Ala-His-Ile-Ile-Ile, MW: 565.3 Da) with angiotensin I-converting enzyme inhibitory and vasodilatory effects that was purified from Styela clava flesh tissue. In the present study, we investigated the metabolic effects of the antihypertensive peptide in skeletal muscle cells. We found that the antihypertensive peptide stimulated glucose uptake in differentiated L6 rat myoblast cells in a dose-dependent manner. Inhibition of AMP-activated protein kinase (AMPK) by compound C significantly inhibited the antihypertensive peptide-stimulated glucose uptake. Western blotting analyses revealed that the antihypertensive peptide stimulated AMPK phosphorylation and this enhancement could be specifically inhibited by compound C. Furthermore, the current study demonstrates that translocation of glucose transporter-4 (GLUT4) to the plasma membrane was stimulated by the antihypertensive peptide. In summary, the findings from this study suggest that the antihypertensive peptide may have beneficial effects on the glucose metabolism in skeletal muscle cells via a mechanism involving AMPK and possible stimulation of the intrinsic activity of GLUT4 transporter.

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References

  1. Carr DB, Utzschneider KM (2004) Intra-abdominal fat is a major determinant of NCEP ATP III criteria for the metabolic syndrome. Diabetes 53:2087–2094

    Article  CAS  Google Scholar 

  2. Hu G, Qiao Q, Tuomilehto J, Eliasson M, Feskens EJ, Pyörälä K (2004) Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies. The DECODE Insulin Study Group. Diabetologia 47:1245–1256

    CAS  Google Scholar 

  3. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867

    Article  CAS  Google Scholar 

  4. Moller DE, Flier JS (1992) Insulin resistance: mechanisms, syndromes, and implications. N Engl J Med 325:938–942

    Google Scholar 

  5. Breen DM, Sanli T, Giacca A, Tsiani E (2008) Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK. Biochem Biophys Res Commun 374:117–122

    Article  CAS  Google Scholar 

  6. Zygmunt K, Faubert B, MacNeil J, Tsiani E (2010) Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK. Biochem Biophys Res Commun 398:178–183

    Article  CAS  Google Scholar 

  7. Stephens JM, Pilch PF (1995) The metabolic regulation and vesicular transport of GLUT4, the major insulin-responsive glucose transporter. Endocr Rev 16:529–546

    CAS  Google Scholar 

  8. Zaid H, Antonescu CN, Randhawa VK, Klip A (2008) Insulin action on glucose transporters through molecular switches, tracks and tethers. Biochem J 413:201–215

    Article  CAS  Google Scholar 

  9. Dugani CB, Randhawa VK, Cheng AW, Patel N, Klip A (2008) Selective regulation of the perinuclear distribution of glucose transporter 4 (GLUT4) by insulin signals in muscle cells. Eur J Cell Biol 87:337–351

    Article  CAS  Google Scholar 

  10. Taniguchi CM, Emanuelli B, Kahn CR (2006) Critical nodes in signaling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7:85–96

    Article  CAS  Google Scholar 

  11. Kim JH, Lee JO, Lee SK, Jung JH, You GY, Park SH, Park M, Kim SD, Kim HS (2010) Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. Life Sci 87:42–48

    Article  CAS  Google Scholar 

  12. Rogers NH, Witczak CA, Hirshman MF, Goodyear LJ, Greenberg AS (2009) Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus. Biochem Biophys Res Commun 382:646–650

    Article  CAS  Google Scholar 

  13. Konrad D, Rudich A, Bilan PJ, Patel N, Richardson C, Witters LA, Klip A (2005) Troglitazone causes acute mitochondrial membrane depolarisation and an AMPK-mediated increase in glucose phosphorylation in muscle cells. Diabetologia 48:954–966

    Article  CAS  Google Scholar 

  14. Zou MH, Kirkpatrick SS, Davis BJ, Nelson JS, Wiles WG, Schlattner U, Neumann D, Brownlee M, Freeman MB, Goldman MH (2004) Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo role of mitochondrial reactive nitrogen species. J Biol Chem 279:43940–43951

    Article  CAS  Google Scholar 

  15. Stump CS, Hamiton MT, Sowers JR (2006) Effect of antihypertensive agents on the development of type 2 diabetes mellitus. Mayo Clin Proc 81:796–806

    Article  CAS  Google Scholar 

  16. Henriksen EJ, Jacob S (2003) Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol 196:171–179

    Article  CAS  Google Scholar 

  17. Ko SC, Lee JK, Byun HG, Lee SC, Jeon YJ (2012) Purification and characterization of angiotensin I-converting enzyme inhibitory peptide from enzymatic hydrolysates of Styela clava flesh tissue. Process Biochem 47:34–40

    Article  CAS  Google Scholar 

  18. Ko SC, Kim DG, Han CH, Lee YJ, Lee JK, Byun HG, Lee SC, Park SJ, Lee DH, Jeon YJ (2012) Nitric oxide-mediated vasorelaxation effects of anti-angiotensin I-converting enzyme (ACE) peptide from Styela clava flesh tissue and its anti-hypertensive effect in spontaneously hypertensive rats. Food Chem 134:1141–1145

    Article  CAS  Google Scholar 

  19. Zimmet P, Alberti K, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787

    Article  CAS  Google Scholar 

  20. Chang MS, Oh MS, Kim DR, Jung KJ, Park S, Choi SB, Ko BS, Park SK (2006) Effects of Okchun-San, a herbal formulation, on blood glucose levels and body weight in a model of type 2 diabetes. J Ethnopharmacol 103:491–495

    Article  Google Scholar 

  21. Jung UJ, Baek NI, Chung HG, Bang MH, Yoo JS, Jeong TS, Lee KT, Kang YJ, Lee MK, Yeo JY, Choi MS (2007) The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice. Food Chem Toxicol 45:2022–2029

    Article  CAS  Google Scholar 

  22. Sarmadi BH, Ismail A (2010) Antioxidant peptides from food proteins: a review. Peptides 31:1949–1956

    Article  CAS  Google Scholar 

  23. Lee SH, Kang SM, Ko SC, Lee DH, Jeon YJ (2012) Octaphlorethol A, a novel phenolic compound isolated from a brown alga, Ishige foliacea, increases glucose transporter 4-mediated glucose uptake in skeletal muscle cells. Biochem Biophys Res Commun 420:576–581

    Article  CAS  Google Scholar 

  24. Lee MS, Hwang JT, Kim S, Yoon S, Kim MS, Yang HJ, Kwon DY (2010) Ginsenoside Rc, an active component of Panax ginseng, stimulates glucose uptake in C2C12 myotubes through an AMPK-dependent mechanism. J Ethnopharmacol 127:771–776

    Article  CAS  Google Scholar 

  25. Ito Y, Obara K, Ikeda R, Ishii M, Tanabe Y, Ishikawa T, Nakayama K (2006) Passive stretching produces Akt-and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice. Pflugers Arch 451:803–813

    Article  CAS  Google Scholar 

  26. Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713

    Article  CAS  Google Scholar 

  27. Raj PA, Dentino AR (2002) Current status of defensins and their role in innate and adaptive immunity. FEMS Microbiol Lett 206:9–18

    Article  CAS  Google Scholar 

  28. Sheetz MJ, King GL (2002) Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA 288:2579–2588

    Article  CAS  Google Scholar 

  29. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vailancourt E, Smith RO, Gorgun CZ, Hotamosligil GS (2006) Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137–1140

    Article  Google Scholar 

  30. Nakatani Y, Kaneto H, Kawamori D, Yoshiuchi K, Hatazaki M, Matsuoka K, Ozawa K, Ogawa S, Hori M, Yamasaki Y, Matsuhisa M (2005) Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J Biol Chem 280:847–851

    Article  CAS  Google Scholar 

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2005479), and also supported Marine Biotechnology Program (20150220) Funded by Ministry of Oceans and Fisheries, Republic of Korea.

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Correspondence to Won-Kyo Jung or You-Jin Jeon.

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Ko, SC., Kim, JI., Park, SJ. et al. Antihypertensive peptide purified from Styela clava flesh tissue stimulates glucose uptake through AMP-activated protein kinase (AMPK) activation in skeletal muscle cells. Eur Food Res Technol 242, 163–170 (2016). https://doi.org/10.1007/s00217-015-2526-7

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