Skip to main content

Advertisement

Log in

Multiplexing detection and measurement of diabetes biomarkers in mice treated with different concentrations of Kappaphycus alvarezii extract

  • Published:
Journal of Applied Phycology Aims and scope Submit manuscript

Abstract

Kappaphycus alvarezii is edible red seaweed from the phylum Rhodophyta. In recent studies, K. alvarezii has demonstrated its beneficial therapeutic properties such as antioxidant, wound-healing, and anticancer properties. This study aimed to investigate the effect of 100 and 200 mg kg−1 K. alvarezii extracts on streptozotocin-induced type II diabetic ICR mice. Changes in plasma glucose level and body weight in mice treated with extracts before and after treatments were evaluated. Stomach tissue and epididymal white adipose tissue (WAT) were excised and ground into fine powder before RNA extraction. The messenger RNA (mRNA) expressions of ghrelin from stomach and resistin from epididymal WAT were measured by quantitative RT-qPCR. Multiplexed immunoassays were performed to analyze protein serum level of diabetic-related biomarkers relative to negative control mice. Kappaphycus alvarezii-treated diabetic mice did not experience significant changes in plasma glucose level and body weight. Interestingly, RT-qPCR analysis reported an opposing effect of 100 and 200 mg kg−1 K. alvarezii on both ghrelin and resistin mRNA expression. The 100 mg kg−1 seaweed extracts upregulated ghrelin mRNA expression while reducing resistin mRNA expression. On the contrary, 200 mg kg−1 seaweed extracts demonstrated opposing action whereby it downregulated ghrelin and upregulated resistin expression levels. Multiplexing analysis of K. alvarezii treatments did not give significant upregulation or downregulation of the diabetic-related biomarkers relative to diabetic control mice. Instead, results from tolbutamide-treated mice have consistently demonstrated its effective antidiabetic activity in each experiment mentioned above. In conclusion, there was insufficient strong evidence to prove that 100 and 200 mg kg−1 K. alvarezii extracts are effective in treating streptozotocin-induced diabetic mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aaboe K, Knop FK, Vilsboll T, Volund A, Simonsen U, Deacon CF, Madsbad S, Holst JJ, Krarup T (2009) KATP channel closure ameliorates the impaired insulinotropic effect of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. J Clin Endocr Metab 94:603–608

    Article  CAS  PubMed  Google Scholar 

  • Boopathy NS, Kathiresan K (2010) Anticancer drugs from marine flora: an overview. J Oncol 2010:1–18

    Article  Google Scholar 

  • Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110

    Article  CAS  PubMed  Google Scholar 

  • Coniff RF, Shapiro JA, Seaton TB, Bray GA (1995) Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin dependent diabetes mellitus. Am J Med 98:443–451

  • Cyriac B, Eswaran K (2016) Anti-hyperglycemic effect of aqueous extract of Kappaphycus alvarezii (Doty) Doty ex. P. Silva in alloxan-induced diabetic rats. J Appl Phycol 28:2507–2513

    Article  Google Scholar 

  • Date Y, Nakazato M, Hasiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S (2002) Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion. Diabetes 51:124–129

    Article  CAS  PubMed  Google Scholar 

  • Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, Eberhardt NL, Kudva YC (2011) Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim 45:131–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dekel Y, Glucksam Y, Elron-Gross I, Margalit R (2009) Insights into modeling streptozotocin-induced diabetes in ICR mice. Lab Anim 38:55–60

    Article  Google Scholar 

  • Denroche HC, Jevi J, Wideman RD, Sequeira RM, Huynh FK, Covey SD, Kieffer TJ (2011) Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes 60:1414–1423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diogo JV, Novo SG, Gonzalez MJ, Ciancia M, Bratanich AC (2015) Antiviral activity of lambda-carrageenan prepared from red seaweed (Gigartina skottsbergii) against BoHV-1 and SuHV-1. Res Vet Sci 98:142144

    Article  Google Scholar 

  • Doty MS (1973) Farming the red seaweed, Eucheuma, for carrageenans. Micronesica 9:59–73

    Google Scholar 

  • Doty MS (1983) Coral reef diversified farming. In: Tseng CK (ed) Proceedings of the Joint China—U.S. Phycology Symposium. Science Press, Beijing, pp 437–478

  • Ebrahimi M, Roudkenar MH, Fooladi AAI, Halabian R, Ghanei M, Kondo H, Nourani MR (2010) Discrepancy between mRNA and protein expression of neutrophil gelatinase-associated lipocalin in bronchial epithelium induced by sulfur mustard. J Biomed Biotechnol 2010:1–6

    Article  Google Scholar 

  • Fard SG, Tan RTR, Mohammed AA, Goh YM, Muhamad KS, AL-Jashamy KA, Mohamed S (2011) Wound healing properties of Eucheuma cottonii extracts in Sprague-Dawley rats. J Med Plants Res 5:6373–6380

    Google Scholar 

  • Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2001) Tumor necrosis factor alpha is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. Biochem Biophys Res Com 288:1027–1031

    Article  CAS  PubMed  Google Scholar 

  • Fujita H, Fujishima H, Morii T, Koshimura J, Narita T, Kakei M, Ito S (2002) Effect of metformin on adipose tissue resistin expression in db/db mice. Biochem Biophys Res Com 298:345–349

    Article  CAS  PubMed  Google Scholar 

  • Fukui Y, Motojima K (2002) Expression of resistin in the adipose tissue is modulated by various factors including peroxisome proliferator-activated receptor alpha. Diabetes Obes Metab 4:342–345

    Article  CAS  PubMed  Google Scholar 

  • Harris RE (ed) (2007) Inflammation in the pathogenesis of chronic diseases: the COX-2 controversy. Springer, Dordrecht, pp 72–77

    Google Scholar 

  • Hurtado AQ, Gerung GS, Yasir S, Critchley AT (2014) Cultivation of tropical red seaweeds in the BIMP-EAGA region. J Appl Phycol 26:707–718

    Article  Google Scholar 

  • Indumathi P, Mehta A (2016) A novel anticoagulant peptide from the Nori hydrolysate. J Funct Foods 20:606–617

    Article  CAS  Google Scholar 

  • Ito Y, Okeda T, Sato Y, Ito M, Sakata T (1996) Plasminogen activator inhibitor-1 in nonobese subjects with non-insulin-dependent diabetes mellitus. Exp Biol Med 211:287–291

    Article  CAS  Google Scholar 

  • Juan CC, Au LC, Fang VS, Kang SF, Ko YH, Kuo SF, Hsu YP, Kwok CF, Ho LT (2001) Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem Biophys Res Com 289:1328–1333

    Article  CAS  PubMed  Google Scholar 

  • Jung HS, Youn BS, Cho YM, Yu KY, Park HJ, Shin CS, Kim SY, Lee HK, Park KS (2005) The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus. Metabol Clin Exp 54:314–320

    Article  CAS  Google Scholar 

  • Khokhar KK, Sidhu S, Kaur G (2013) Relationship between serum leptin and type 2 diabetes mellitus and their association with obesity and menopausal status. Arch Appl Sc Res 5:38–44

    CAS  Google Scholar 

  • Kieffer TJ, Heller RS, Leech CA, Holz GG, Habener JF (1997) Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 46:1087–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krarup T (1988) Immunoreactive gastric inhibitory polypeptide. Endocr Rev 9:122–134

    Article  CAS  PubMed  Google Scholar 

  • Le Lay S, Boucher J, Rey A, Castan-Laurell I, Krief S, Ferre P, Valet P, Dugail I (2001) Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem Biophys Res Com 289:564–567

  • Lee JW, Wang JH, Ng KM, Tan CH, Rabina P, Teo SS (2015) In-vitro anticancer activity of Eucheuma cottonii extracts against Hela cell line, human lung carcinoma cell line (SK-LU-1), human colon carcinoma cell line (HCT-116), and fibroblast. Int J Curr Multidiscip Stud 1:69–73

    Google Scholar 

  • Li WL, Zheng HC, Bukuru J, De Kimpe N (2004) Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J Ethnopharmacol 92:1–21

    Article  CAS  PubMed  Google Scholar 

  • Mansor LS, Gonzalex ER, Cole MA, Tyler DJ, Beeson JH, Clarke K, Carr CA, Heather LC (2013) Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose. Cardiovasc Diabetol 12:136

    Article  PubMed  PubMed Central  Google Scholar 

  • McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S (2003) Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocr Metab 88:6098–6106

    Article  CAS  PubMed  Google Scholar 

  • Mizuno TM, Berge H, Funabashi T, Kleopoulos SP, Zhong YG, Bauman WA, Mobbs CV (1996) Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity. Proc Natl Acad Sci U S A 93:3434–3438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Msuya FE, Buriyo A, Omar I, Pascal B, Narrain K, Ravina JJM, Mrabu E, Wakibia JG (2014) Cultivation and utilisation of red seaweeds in the Western Indian Ocean (WIO) Region. J Appl Phycol 26:699–705

    Article  CAS  Google Scholar 

  • Nagarani N, Kumaraguru AK (2013) Evaluation of anti-inflammatory, antidiabetic, cytotoxic activity of Kappaphycus alvarezii. Int J Pharma Bio Sci 4:921–929

    Google Scholar 

  • Namvar F, Mohamed S, Fard SG, Behravan J, Mustapha NM, Alitheen NBM, Othman F (2012) Polyphenol-rich seaweed (Eucheuma cottonii) extract suppresses breast tumour via hormone modulation and apoptosis induction. Food Chem 130:376–382

    Article  CAS  Google Scholar 

  • Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B (2006) Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the study of diabetes. Diabetes Care 29:1963–1972

    Article  PubMed  Google Scholar 

  • Patel L, Buckles AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA (2003) Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Com 300:472–476

    Article  CAS  PubMed  Google Scholar 

  • Poon M, Hussain K (2007) Postprandial hyperinsulinaemic hypoglycaemia and type 1 diabetes mellitus. Arch Dis Child 92:714–715

    Article  PubMed  PubMed Central  Google Scholar 

  • Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM (2000) A new rat model of type 2 diabetes: the fat-fed streptozotocin-treated rat. Metabolis 49:1390–1394

    Article  CAS  Google Scholar 

  • Reimann F, Gribble FM (2002) Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes 51:2757–2763

    Article  CAS  PubMed  Google Scholar 

  • Shan X, Liu X, Hao J, Cai C, Fan F, Dun Y, Zhao X, Liu X, Li C, Yu G (2016) In vitro and in vivo hypoglycemic effects of brown algal fucoidans. Int J Biol Macromol 82:249–255

    Article  CAS  PubMed  Google Scholar 

  • Sonmez MF, Karabulut D, Kilic E, Akalin H, Sakalar C, Gunduz Y, Kara A, Dundar M (2015) The effects of streptozotocin-induced diabetes on ghrelin expression in rat testis: biochemical and immnohistochemical study. Folia Histochem Cytol 53:26–34

    Article  CAS  Google Scholar 

  • Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 52:313–320

    Article  CAS  PubMed  Google Scholar 

  • Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312

    Article  CAS  PubMed  Google Scholar 

  • Tahrani AA, Piya MK, Kennedy A, Barnett AH (2010) Glycaemic control in type 2 diabetes: targets and new therapies. Pharmacol Therapeut 125:328361

    Article  Google Scholar 

  • Takahashi K, Hosokawa M, Kasajima H, Hatanaka K, Kudo K, Shimoyama N, Miyashita K (2015) Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues. Oncol Lett 10:14631467

    Google Scholar 

  • Tam SF, Lian AA, Kuppusamy P, Yusoff MM, Govindan N (2013) Studies on in-vitro antioxidant activity of marine edible seaweeds from the east coastal region of Peninsular Malaysia using different extraction methods. J Coastal Life Med 1:193–198

    Google Scholar 

  • Toyoshima Y, Gavrilova O, Yakar S, Jou W, Pack S, Asghar Z, Wheeler MB, LeRoith D (2005) Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes. Endocrinology 146:4024–4035

    Article  CAS  PubMed  Google Scholar 

  • Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609–613

    Article  CAS  PubMed  Google Scholar 

  • Vollmer K, Holst JJ, Baller B, Ellrichmann M, Nauck MA, Schmidt WE, Meier JJ (2012) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57:678–687

    Article  Google Scholar 

  • Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS (2001) Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 276:25651–25653

    Article  CAS  PubMed  Google Scholar 

  • Zemke-White WL, Ohno M (1999) World seaweed utilization: an end-of-century summary. J Appl Phycol 11:369–376

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. S. Teo.

Ethics declarations

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J.H., Lee, J.W., Lim, L.H. et al. Multiplexing detection and measurement of diabetes biomarkers in mice treated with different concentrations of Kappaphycus alvarezii extract. J Appl Phycol 29, 2097–2106 (2017). https://doi.org/10.1007/s10811-017-1121-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10811-017-1121-7

Keywords

Navigation