Nutr Res Pract.  2015 Oct;9(5):472-479. 10.4162/nrp.2015.9.5.472.

Sargassum coreanum extract alleviates hyperglycemia and improves insulin resistance in db/db diabetic mice

• Park MH
• Nam YH
• Han JS

• KMID: 2313867
• DOI: http://doi.org/10.4162/nrp.2015.9.5.472

Abstract

BACKGROUND/OBJECTIVES
The goal of this study was to examine the effect of Sargassum coreanum extract (SCE) on blood glucose concentration and insulin resistance in C57BL-KsJ-db/db mice.
MATERIALS/METHODS
For 6 weeks, male C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone (0.005%, w/w).
RESULTS
A supplement of the SCE for 6 weeks induced a significant reduction in blood glucose and glycosylated hemoglobin concentrations, and it improved hyperinsulinemia compared to the diabetic control db/db mice. The glucokinase activity in the hepatic glucose metabolism increased in the SCE-supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities in the SCE-supplemented db/db mice were significantly lower than those in the diabetic control db/db mice. The homeostatic index of insulin resistance was lower in the SCE-supplemented db/db mice than in the diabetic control db/db mice.
CONCLUSIONS
These results suggest that a supplement of the SCE lowers the blood glucose concentration by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.

Keyword

Anti-diabetic effects; Sargassum coreanum extract; C57BL/KsJ-db/db mice; hyperglycemia; insulin resistance

MeSH Terms

Animals
Blood Glucose
Glucokinase
Glucose
Glucose-6-Phosphatase
Hemoglobin A, Glycosylated
Humans
Hyperglycemia*
Hyperinsulinism
Insulin Resistance*
Insulin*
Male
Metabolism
Mice*
Phosphoenolpyruvate
Sargassum*
Blood Glucose
Glucokinase
Glucose
Glucose-6-Phosphatase
Insulin
Phosphoenolpyruvate

Figure

• 

  Fig. 1 Changes in the blood glucose concentrations of C57BL/KsJ-db/db mice supplemented with SCE for 6 weeks. DMC: C57BL/KsJ-db/db mice supplemented with AIN-93G diet; rosiglitazone: C57BL/KsJ-db/db mice supplemented with rosiglitazone (0.005 g/100 g diet); SCE: C57BL/KsJ-db/db mice supplemented with SCE (0.5 g/100 g diet). Values are mean ± SD (n = 8); Superscripts with different alphabets in same time point differ significantly at P < 0.05 as analyzed via ANOVA with Duncan's multiple range test.

• 

  Fig. 2 The effect of SCE supplement on glucose tolerance test in C57BL/KsJ-db/db mice. After a 12 h fast, male mice were intraperitoneally injected with glucose (0.5 g/kg body weight). The blood glucose concentration was measured at the indicated times and presented as actual value injection. DMC: C57BL/KsJ-db/db mice supplemented with AIN-93G diet; rosiglitazone: C57BL/KsJ-db/db mice supplemented with rosiglitazone (0.005 g/100 g diet); SCE: C57BL/KsJ-db/db mice supplemented with SCE (0.5 g/100 g diet). Values are mean ± SD (n = 8); Superscripts with different alphabets in same time point differ significantly at P < 0.05 as analyzed via ANOVA with Duncan's multiple range test.

• 

  Fig. 3 The effects of SCE supplementation on the hepatic glucokinase (A), glucose-6-phosphatase (B), and phosphoenolpyruvate carboxykinase activities (C), and glycogen content (D) in C57BL/KsJ-db/db mice. DMC: C57BL/KsJ-db/db mice supplemented with AIN-93G diet; rosiglitazone: C57BL/KsJ-db/db mice supplemented with rosiglitazone (0.005 g/100 g diet); SCE: C57BL/KsJ-db/db mice supplemented with SCE (0.5 g/100 g diet). Values are mean ± SD (n = 8); Superscripts with different alphabets differ significantly at P < 0.05 as analyzed via Duncan's multiple range test.

Reference

1. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414:782–787.

2. Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS. The skin. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia (PA): Elsevier Saunders;2005. p. 1194–1195.

3. DeBruyne LK, Whitney EN, Pinna K. Nutrition and Diet Therapy. 7th ed. Belmont (CA): Thomson Wadsworth;2008.

4. Kobayashi M, Iwanishi M, Egawa K, Shigeta Y. Pioglitazone increases insulin sensitivity by activating insulin receptor kinase. Diabetes. 1992; 41:476–483.

5. Min KH, Kim HJ, Jeon YJ, Han JS. Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL/KsJ-db/db mice. Diabetes Res Clin Pract. 2011; 93:70–76.

6. Halliwell B, Gutteridge JM. Antioxidant defences. Free Radicals in Biology and Medicine. 3rd ed. Oxford: Oxford University Press;1999. p. 105–159.

7. Lee IK, Kang JW. Check list of the marine Algae in Korea. Korean J Phycol. 1986; 1:311–325.

8. Zou Y, Qian ZJ, Li Y, Kim MM, Lee SH, Kim SK. Antioxidant effects of phlorotannins isolated from Ishige okamurae in free radical mediated oxidative systems. J Agric Food Chem. 2008; 56:7001–7009.

9. Ahn MJ, Yoon KD, Kim CY, Kim JH, Shin CG, Kim J. Inhibitory activity on HIV-1 reverse transcriptase and integrase of a carmalol derivative from a brown Alga, Ishige okamurae. Phytother Res. 2006; 20:711–713.

10. Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care. 1997; 20:1087–1092.

11. 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; 85:2402–2410.

12. Kwak CS, Kwak JS. Cell fractionation method of the rat liver. Keimyung Med J. 1986; 5:45–53.

13. Davidson AL, Arion WJ. Factors underlying significant underestimations of glucokinase activity in crude liver extracts: physiological implications of higher cellular activity. Arch Biochem Biophys. 1987; 253:156–167.

14. Alegre M, Ciudad CJ, Fillat C, Guinovart JJ. Determination of glucose-6-phosphatase activity using the glucose dehydrogenase-coupled reaction. Anal Biochem. 1988; 173:185–189.

15. Bentle LA, Lardy HA. Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase. J Biol Chem. 1976; 251:2916–2921.

16. Seifter S, Dayton S, Novic B, Muntwyler E. The estimation of glycogen with the anthrone reagent. Arch Biochem. 1950; 25:191–200.

17. Kim DJ, Jeong YJ, Kwon JH, Moon KD, Kim HJ, Jeon SM, Lee MK, Park YB, Choi MS. Beneficial effect of chungkukjang on regulating blood glucose and pancreatic beta-cell functions in C75BL/KsJ-db/db mice. J Med Food. 2008; 11:215–223.

18. Simon SF, Taylor CG. Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood). 2001; 226:43–51.

19. 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; 37:1549–1558.

20. Cantello BC, Cawthorne MA, Haigh D, Hindley RM, Smith SA, Thurlby PL. The synthesis of BRL 49653 - a novel and potent antihyperglycemic agent. Bioorg Med Chem Lett. 1994; 4:1181–1184.

21. Kim KR, Lee JH, Kim SJ, Rhee SD, Jung WH, Yang SD, Kim SS, Ahn JH, Cheon HG. KR-62980: a novel peroxisome proliferator-activated receptor gamma agonist with weak adipogenic effects. Biochem Pharmacol. 2006; 72:446–454.

22. Baron AD. Postprandial hyperglycaemia and alpha-glucosidase inhibitors. Diabetes Res Clin Pract. 1998; 40:Suppl. S51–S55.

23. DeFronzo RA, Gunnarsson R, Björkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J Clin Invest. 1985; 76:149–155.

24. Van Gaal LF, De Leeuw IH. Rationale and options for combination therapy in the treatment of type 2 diabetes. Diabetologia. 2003; 46:Suppl 1. M44–M50.

25. Tahara Y, Shima K. Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care. 1995; 18:440–447.

26. Fujiwara T, Wada M, Fukuda K, Fukami M, Yoshioka S, Yoshioka T, Horikoshi H. Characterization of CS-045, a new oral antidiabetic agent, II. Effects on glycemic control and pancreatic islet structure at a late stage of the diabetic syndrome in C57BL/KsJ-db/db mice. Metabolism. 1991; 40:1213–1218.

27. Patel J, Miller E, Hu J, Granett J. BRL 49653 (a thiazolidinedione) improves glycemic control in NIDDM patients. Diabetes. 1997; 46:150A.

28. Uno T, Ohsawa I, Tokudome M, Sato Y. Effects of Goshajinkigan on insulin resistance in patients with type 2 diabetes. Diabetes Res Clin Pract. 2005; 69:129–135.

29. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000; 23:57–63.

30. Shaw JE, Hodge AM, De Courten M, Chitson P, Zimmet PZ. Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality. Diabetologia. 1999; 42:1050–1054.

31. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999; 22:920–924.

32. Perry RC, Baron AD. Impaired glucose tolerance. Why is it not a disease? Diabetes Care. 1999; 22:883–885.

33. Zimmet PZ, Alberti KG. The changing face of macrovascular disease in non-insulin-dependent diabetes mellitus: an epidemic in progress. Lancet. 1997; 350:Suppl 1. SI1–SI4.

34. Basu A, Basu R, Shah P, Vella A, Johnson CM, Jensen M, Nair KS, Schwenk WF, Rizza RA. Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity. Diabetes. 2001; 50:1351–1362.

35. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992; 15:318–368.

36. Coleman DL, Hummel KP. Studies with the mutation, diabetes, in the mouse. Diabetologia. 1967; 3:238–248.

37. Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, Shelton KD, Lindner J, Cherrington AD, Magnuson MA. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem. 1999; 274:305–315.

38. Nordlie RC, Bode AM, Foster JD. Recent advances in hepatic glucose 6-phosphatase regulation and function. Proc Soc Exp Biol Med. 1993; 203:274–285.

39. Mithieux G. New knowledge regarding glucose-6 phosphatase gene and protein and their roles in the regulation of glucose metabolism. Eur J Endocrinol. 1997; 136:137–145.

40. Robinson C, Tamborlane WV, Maggs DG, Enoksson S, Sherwin RS, Silver D, Shulman GI, Caprio S. Effect of insulin on glycerol production in obese adolescents. Am J Physiol. 1998; 274:E737–E743.

41. Boden G. Interaction between free fatty acids and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2002; 5:545–549.

42. Park SA, Choi MS, Cho SY, Seo JS, Jung UJ, Kim MJ, Sung MK, Park YB, Lee MK. Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci. 2006; 79:1207–1213.

43. Park SA, Choi MS, Kim MJ, Jung UJ, Kim HJ, Park KK, Noh HJ, Park HM, Park YB, Lee JS, Lee MK. Hypoglycemic and hypolipidemic action of Du-zhong (Eucommia ulmoides Oliver) leaves water extract in C57BL/KsJ-db/db mice. J Ethnopharmacol. 2006; 107:412–417.

44. Jung UJ, Baek NI, Chung HG, Bang MH, Jeong TS, Lee KT, Kang YJ, Lee MK, Kim HJ, Yeo J, Choi MS. Effects of the ethanol extract of the roots of Brassica rapa on glucose and lipid metabolism in C57BL/KsJ-db/db mice. Clin Nutr. 2008; 27:158–167.