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Stimulatory Effect of Balanced Deep-Sea Water Containing Chitosan Oligosaccharides on Glucose Uptake in C2C12 Myotubes

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Abstract

Deep-sea water (DSW) and chitosan oligosaccharides (COS) have recently drawn much attention because of their potential medical and pharmaceutical applications. Balanced DSW (BDSW) was prepared by mixing DSW mineral extracts and desalinated water. This study investigated the effects of BDSW, COS, and BDSW containing COS on glucose uptake and their mode of action in mature C2C12 myotubes. BDSW and COS increased glucose uptake in a dose-dependent manner. BDSW containing COS synergistically increased glucose uptake; this was dependent on the activation of insulin receptor substrate 1 and protein kinase C in insulin-dependent signaling pathways as well as liver kinase B1, AMP-activated protein kinase, and mammalian target of rapamycin in insulin-independent signaling pathways. Quantitative real-time polymerase chain reaction revealed that the expressions of the following genes related to glucose uptake were elevated: glucose transporter 4 (GLUT4), insulin-responsive aminopeptidase, and vesicle-associated membrane protein 2 for abundant proteins of GLUT4 storage vesicles (GSVs); syntaxin 4 and soluble N-ethylmaleimide-sensitive factor attachment protein 23 for trafficking between the plasma membrane and GSVs; and syntaxin 6 and syntaxin 16 for trafficking between GSVs and the trans-Golgi network. Taken together, these results suggest BDSW containing COS has a greater stimulatory effect on glucose uptake than BDSW or COS alone. Moreover, this effect is mediated by the stimulation of diverse signaling pathways via the activation of main signaling molecules related to GSV trafficking.

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Abbreviations

DSW:

Deep-sea water

BDSW:

Balanced deep-sea water

COS:

Chitosan oligosaccharides

GSVs:

GLUT 4 storage vesicles

IRS-1:

Insulin receptor substrate 1

PI3-K:

Phosphatidylinositol 3-kinase

PKC:

Protein kinase C

LKB1:

Liver kinase B1

AMPK:

AMP-activated protein kinase

mTOR:

Mammalian target of rapamycin

Sirt1:

Sirtuin 1

GLUT4:

Glucose transporter 4

IRAP:

Insulin-responsive aminopeptidase

VAMP2:

Vesicle-associated membrane protein 2

SNAP23:

Soluble N-ethylmaleimide-sensitive factor attachment protein 23

SNARES:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

TGN:

trans-Golgi network

NSF:

N-Ethylmaleimide-sensitive factor

Syn 4:

Syntaxin 4

Syn 6:

Syntaxin 6

Syn 16:

Syntaxin 16

References

  • Bell DS (2006) The case for combination therapy as first-line treatment for the type 2 diabetic patient. Treat Endocrinol 5:131–137

    Article  CAS  PubMed  Google Scholar 

  • Bell DS (2013) Combine and conquer: advantages and disadvantages of fixed-dose combination therapy. Diabetes Obes Metab 15:291–300

    Article  CAS  PubMed  Google Scholar 

  • Bjornholm M, Kawano Y, Lehtihet M, Zierath JR (1997) Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation. Diabetes 46:524–527

    Article  CAS  PubMed  Google Scholar 

  • Bogan JS (2012) Regulation of glucose transporter translocation in health and diabetes. Annu Rev Biochem 81:507–532

    Article  CAS  PubMed  Google Scholar 

  • Choi CR, Kim EK, Kim YS, Je JY, An SH, Lee JD, Wang JH, Ki SS, Jeon BT, Moon SH, Park PJ (2012a) Chitooligosaccharides decreases plasma lipid levels in healthy men. Int J Food Sci Nutr 63:103–106

    Article  CAS  PubMed  Google Scholar 

  • Choi EH, Yang HP, Chun HS (2012b) Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation. Nutr Res 32:218–228

    Article  CAS  PubMed  Google Scholar 

  • Clark TA, Deniset JF, Heyliger CE, Pierce GN (2014) Alternative therapies for diabetes and its cardiac complications: role of vanadium. Heart Fail Rev 19:123–132

    Article  CAS  PubMed  Google Scholar 

  • Copps KD, White MF (2012) Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 55:2565–2582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornu M, Albert V, Hall MN (2013) mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev 23:53–62

    Article  CAS  PubMed  Google Scholar 

  • Destefano MA, Jacinto E (2013) Regulation of insulin receptor substrate-1 by mTORC2 (mammalian target of rapamycin complex 2). Biochem Soc Trans 41:896–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu ZY, Yang FL, Hsu HW, Lu YF (2012) Drinking deep seawater decreases serum total and low-density lipoprotein-cholesterol in hypercholesterolemic subjects. J Med Food 15:535–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ha BG, Shin EJ, Park JE, Shon YH (2013) Anti-diabetic effect of balanced deep-sea water and its mode of action in high-fat diet induced diabetic mice. Mar Drugs 11:4193–4212

    Article  PubMed  PubMed Central  Google Scholar 

  • Ha BG, Park JE, Shin EJ, Shon YH (2014a) Modulation of glucose metabolism by balanced deep-sea water ameliorates hyperglycemia and pancreatic function in streptozotocin-induced diabetic mice. PLoS One 9:e102095

    Article  PubMed  PubMed Central  Google Scholar 

  • Ha BG, Park JE, Shin EJ, Shon YH (2014b) Effects of balanced deep-sea water on adipocyte hypertrophy and liver steatosis in high-fat, diet-induced obese mice. Obesity (Silver Spring) 22:1669–1678

    Article  CAS  Google Scholar 

  • Hardie DG (2013) AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes 62:2164–2172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hataguchi Y, Tai H, Nakajima H, Kimata H (2005) Drinking deep-sea water restores mineral imbalance in atopic eczema/dermatitis syndrome. Eur J Clin Nutr 59:1093–1096

    Article  CAS  PubMed  Google Scholar 

  • He S, Hao J, Peng W, Qiu P, Li C, Guan H (2014) Modulation of lipid metabolism by deep-sea water in cultured human liver (HepG2) cells. Mar Biotechnol (NY) 16(2):219–229

  • Huang S, Czech MP (2007) The GLUT4 glucose transporter. Cell Metab 5:237–252

    Article  CAS  PubMed  Google Scholar 

  • Hung HY, Qian K, Morris-Natschke SL, Hsu CS, Lee KH (2012) Recent discovery of plant-derived anti-diabetic natural products. Nat Prod Rep 29:580–606

    Article  CAS  PubMed  Google Scholar 

  • Hwang HS, Kim HA, Lee SH, Yun JW (2009a) Anti-obesity and antidiabetic effects of deep sea water on ob/ob mice. Mar Biotechnol (NY) 11:531–539

    Article  CAS  Google Scholar 

  • Hwang HS, Kim SH, Yoo YG, Chu YS, Shon YH, Nam KS, Yun JW (2009b) Inhibitory effect of deep-sea water on differentiation of 3T3-L1 adipocytes. Mar Biotechnol (NY) 11:161–168

    Article  CAS  Google Scholar 

  • Je JY, Kim SK (2012) Chitooligosaccharides as potential nutraceuticals: production and bioactivities. Adv Food Nutr Res 65:321–336

    Article  PubMed  Google Scholar 

  • Jo SH, Ha KS, Moon KS, Kim JG, Oh CG, Kim YC, Apostolidis E, Kwon YI (2013) Molecular weight dependent glucose lowering effect of low molecular weight chitosan oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model. Int J Mol Sci 14:14214–14224

    Article  PubMed  PubMed Central  Google Scholar 

  • Ju C, Yue W, Yang Z, Zhang Q, Yang X, Liu Z, Zhang F (2010) Antidiabetic effect and mechanism of chitooligosaccharides. Biol Pharm Bull 33:1511–1516

    Article  CAS  PubMed  Google Scholar 

  • Jung DW, Ha HH, Zheng X, Chang YT, Williams DR (2011) Novel use of fluorescent glucose analogues to identify a new class of triazine-based insulin mimetics possessing useful secondary effects. Mol BioSyst 7:346–358

    Article  CAS  PubMed  Google Scholar 

  • Katsuda S, Yasukawa T, Nakagawa K, Miyake M, Yamasaki M, Katahira K, Mohri M, Shimizu T, Hazama A (2008) Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Biol Pharm Bull 31:38–44

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Chun SY, Lee DH, Lee KS, Nam KS (2013) Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines. Int J Oncol 43:1691–1700

    CAS  PubMed  Google Scholar 

  • Leto D, Saltiel AR (2012) Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol 13:383–396

    Article  CAS  PubMed  Google Scholar 

  • Liu HY, Liu MC, Wang MF, Chen WH, Tsai CY, Wu KH, Lin CT, Shieh YH, Zeng R, Deng WP (2013) Potential osteoporosis recovery by deep sea water through bone regeneration in SAMP8 mice. Evid Based Complement Alternat Med 2013:161976

    PubMed  PubMed Central  Google Scholar 

  • Miao X, Sun W, Fu Y, Miao L, Cai L (2013) Zinc homeostasis in the metabolic syndrome and diabetes. Front Med 7:31–52

    Article  PubMed  Google Scholar 

  • Ni HX, Yu NJ, Yang XH (2010) The study of ginsenoside on PPARgamma expression of mononuclear macrophage in type 2 diabetes. Mol Biol Rep 37:2975–2979

    Article  CAS  PubMed  Google Scholar 

  • Radhakrishnan G, Yamamoto M, Maeda H, Nakagawa A, Kataregopalrao R, Okada H, Nishimori H, Wariishi S, Toda E, Ogawa H, Sasaguri S (2009) Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression. Biochem Biophys Res Commun 387:25–30

    Article  CAS  PubMed  Google Scholar 

  • Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S (2013) Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 1:CD009671

    PubMed  Google Scholar 

  • Rehder D (2012) The potentiality of vanadium in medicinal applications. Future Med Chem 4:1823–1837

    Article  CAS  PubMed  Google Scholar 

  • Resnick LM (1992) Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. Am J Med 93:11S–20S

    Article  CAS  PubMed  Google Scholar 

  • Richter EA, Hargreaves M (2013) Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 93:993–1017

    Article  CAS  PubMed  Google Scholar 

  • Robertson DS (2006) Magnesium or calcium hypophosphite could be a treatment for obesity in humans. Med Hypotheses 66:439–440

    Article  CAS  PubMed  Google Scholar 

  • Ruderman NB, Carling D, Prentki M, Cacicedo JM (2013) AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 123:2764–2772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sajan MP, Bandyopadhyay G, Miura A, Standaert ML, Nimal S, Longnus SL, Van Obberghen E, Hainault I, Foufelle F, Kahn R, Braun U, Leitges M, Farese RV (2010) AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC. Am J Physiol Endocrinol Metab 298:E179–E192

    Article  CAS  PubMed  Google Scholar 

  • Squadrito F, Marini H, Bitto A, Altavilla D, Polito F, Adamo EB, D’anna R, Arcoraci V, Burnett BP, Minutoli L, Di Benedetto A, Di Vieste G, Cucinotta D, De Gregorio C, Russo S, Corrado F, Saitta A, Irace C, Corrao S, Licata G (2013) Genistein in the metabolic syndrome: results of a randomized clinical trial. J Clin Endocrinol Metab 98:3366–3374

    Article  CAS  PubMed  Google Scholar 

  • Stockli J, Fazakerley DJ, James DE (2011) GLUT4 exocytosis. J Cell Sci 124:4147–4159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tahrani AA, Piya MK, Kennedy A, Barnett AH (2010) Glycaemic control in type 2 diabetes: targets and new therapies. Pharmacol Ther 125:328–361

    Article  CAS  PubMed  Google Scholar 

  • Tripathy D, Chavez AO (2010) Defects in insulin secretion and action in the pathogenesis of type 2 diabetes mellitus. Curr Diab Rep 10:184–191

    Article  CAS  PubMed  Google Scholar 

  • Vouri SM, Shaw RF, Waterbury NV, Egge JA, Alexander B (2011) Prevalence of achievement of A1c, blood pressure, and cholesterol (ABC) goal in veterans with diabetes. J Manag Care Pharm 17:304–312

    PubMed  Google Scholar 

  • Yamada E, Lee TW, Pessin JE, Bastie CC (2010) Targeted therapies of the LKB1/AMPK pathway for the treatment of insulin resistance. Future Med Chem 2:1785–1796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan WP, Liu B, Liu CH, Wang XJ, Zhang MS, Meng XM, Xia XK (2009) Antioxidant activity of chito-oligosaccharides on pancreatic islet cells in streptozotocin-induced diabetes in rats. World J Gastroenterol 15:1339–1345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yun JW (2010) Possible anti-obesity therapeutics from nature—a review. Phytochemistry 71:1625–1641

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, Pan HN, Kong WJ, Jiang JD (2010a) Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 59:285–292

    Article  PubMed  Google Scholar 

  • Zhang J, Xia W, Liu P, Cheng Q, Tahirou T, Gu W, Li B (2010b) Chitosan modification and pharmaceutical/biomedical applications. Mar Drugs 8:1962–1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was financially supported by the National R&D project of “Development of new application technology for deep seawater industry” supported by the Ministry of Oceans and Fisheries of the Republic of Korea and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0001).

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  1. Bio-Medical Research Institute, Kyungpook National University Hospital, 50 Samduk 2ga Jung-gu, Daegu, 700-721, South Korea

    Byung Geun Ha, Jung-Eun Park & Yun Hee Shon

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  1. Byung Geun Ha
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Correspondence to Yun Hee Shon.

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Ha, B.G., Park, JE. & Shon, Y.H. Stimulatory Effect of Balanced Deep-Sea Water Containing Chitosan Oligosaccharides on Glucose Uptake in C2C12 Myotubes. Mar Biotechnol 18, 475–484 (2016). https://doi.org/10.1007/s10126-016-9709-5

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