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Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats

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Abstract

Background

We previously reported that Chungkookjang (CKJ), fermented unsalted soybeans, exhibited better anti-diabetic action than cooked soybeans (CSB) in vitro, but its effectiveness and mechanism have not been studied in vivo.

Aim of the study

We investigated whether CKJ modulated insulin resistance, insulin secretion, and pancreatic β-cell growth and survival in 90% pancreatectomized (Px) diabetic rats.

Methods

The Px rats weighing 201 ± 12 g were divided into four groups and fed for 8 weeks with a CSB diet, a CKJ diet, a casein diet, or a casein diet plus rosiglitazone (20 mg/kg body weight/day). With the exception of protein sources and contents of isoflavonoid aglycones and glycosides, the composition of the diets was made identical by adding soybean oil and cellulose to a casein diet. At the end of the experimental periods, hyperglycemic clamp was performed in conscious, unstressed and overnight fasted Px rats to measure insulin secretion capacity. Insulin/IGF-1 signaling was measured by immunoblotting in isolated islets from the treated rats, and β-cell mass, proliferation and apoptosis were also determined by immunohistochemistry.

Results

After 8-week administration, CSB did not modulate glucose-stimulated insulin secretion, but surprisingly, CKJ enhanced insulin secretion. In addition, CKJ potentiated insulin/IGF-1 signaling in islets via the induction of insulin receptor substrate-2 expression, leading to increasing pancreatic duodenal homeobox-1, insulin promoter transcription factor. In parallel with the enhancement of the signaling, CKJ elevated pancreatic β-cell hyperplasia by increasing its proliferation and decreasing apoptosis, whereas CSB did not.

Conclusion

Based on these results, the fermentation of soybeans predominantly with Bacillus subtilis generated isoflavonoid aglycones and small peptides, which improved insulinotropic action in islets of type 2 diabetic rats. Overall, the anti-diabetic action of CKJ was superior to CSB in type 2 diabetic rats.

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References

  1. Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 46:3–19

    Article  CAS  Google Scholar 

  2. Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, Terauchi Y, Ueki K, Kaburagi Y, Satoh S, Sekihara H, Yoshioka Y, Horikoshi H, Furuta Y, Ikawa Y, Kasuga M, Yazaki Y, Aizawa S (1994) Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372:182–186

    Article  CAS  Google Scholar 

  3. Bhathena SJ, Velasquez MT (2002) Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr 76:1191–1201

    CAS  Google Scholar 

  4. Nakajima N, Nozaki N, Ishihara K, Ishikawa A, Tsuji H (2005) Analysis of isoflavone content in tempeh, a fermented soybean, and preparation of a new isoflavone-enriched tempeh. J Biosci Bioeng 100:685–687

    Article  CAS  Google Scholar 

  5. Slavin JL, Karr SC, Hutchins AM, Lampe Jw (1998) Influence of soybean processing, habitual diet and soy dose on urinary isoflavonoid excretion. Am J Clin Nutr 68:S1492–S1495

    Google Scholar 

  6. Kwon DY, Jang JS, Lee JE, Kim YS, Shin DH, Park S (2006) The isoflavonoid aglycone-rich fractions of Chungkookjang, fermented unsalted soybeans, enhance insulin signaling and peroxisome proliferator-activated receptor-γ activity in vitro. Biofactors 26:1–14

    Google Scholar 

  7. Hosokawa YA, Hosokawa H, Chen C, Leahy JL (1996) Mechanism of impaired glucose-potentiated insulin secretion in diabetic 90% pancreatectomy rats. Study using glucagons like peptide-1 (7–37). J Clin Invest 97:180–186

    Article  CAS  Google Scholar 

  8. Harrity T, Farrelly D, Tieman A, Chu C, Kunselman L, Gu L, Ponticiello R, Cap M, Qu F, Shao C, Wang W, Zhang H, Fenderson W, Chen S, Devasthale P, Jeon Y, Seethala R, Yang WP, Ren J, Zhou M, Ryono D, Biller S, Mookhtiar KA, Wetterau J, Gregg R, Cheng PT, Hariharan N (2006) Muraglitazar, a novel dual (alpha/gamma) peroxisome proliferator-activated receptor activator, improves diabetes and other metabolic abnormalities and preserves beta-cell function in db/db mice. Diabetes 55:240–248

    Article  CAS  Google Scholar 

  9. Pfutzner A, Schondorf T, Seidel D, Winkler K, Matthaei S, Hamann A, Forst T (2006) Impact of rosiglitazone on beta-cell function, insulin resistance, and adiponectin concentrations: results from a double-blind oral combination study with glimepiride. Metabolism 55:20–25

    Article  CAS  Google Scholar 

  10. Report of the American Institute of Nutrition (1997) Ad Hoc committee on standards for nutritional studies. J Nutr 107:1340–1348

    Google Scholar 

  11. Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y, Uchino H, Giacca A, McGarry JD (2002) The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51:1825–1833

    CAS  Google Scholar 

  12. Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, Zakaria M, Mossa-Basha M, White MF (2003) Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest 112:1521–1532

    Article  CAS  Google Scholar 

  13. Choi SB, Jang JS, Park S (2005) Estrogen and exercise may enhance beta-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats. Endocrinology 146:4786–4794

    Article  CAS  Google Scholar 

  14. Rooman I, Lardon J, Bouwens L (2002) Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes 51:686–690

    CAS  Google Scholar 

  15. Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, White MF (2004) Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J Clin Invest 114:908–916

    Article  CAS  Google Scholar 

  16. Park S, Dong X, Fisher TL, Dunn SL, Omer AK, Weir G, White MF (2006) Exendin-4 promotes IRS2 signaling to mediate pancreatic beta-cell growth and function. J Biol Chem 281:1159–1168

    Article  CAS  Google Scholar 

  17. Committee of SAS Institute (1985) Guide for personal computers. SAS Institutes Inc, Cary, NC, pp 257–260

    Google Scholar 

  18. Muzumdar R, Ma X, Atzmon G, Vuguin P, Yang X, Barzilai N (2004) Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action. Diabetes 53:441–446

    CAS  Google Scholar 

  19. Guillon F, Champ MM (2002) Carbohydrate fractions of legumes: uses in human nutrition and potential for health. Br J Nutr 88:S293–S306

    Article  CAS  Google Scholar 

  20. Omoni AO, Aluko RE (2005) Soybean foods and their benefits: potential mechanisms of action. Nutr Rev 63:272–283

    Article  Google Scholar 

  21. Bhathena SJ, Velasquez MT (2002) Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr 76:1191–1201

    CAS  Google Scholar 

  22. Haber EP, Ximenes HM, Procopio J, Carvalho CR, Curi R, Carpinelli AR (2003) Pleiotropic effects of fatty acids on pancreatic beta-cells. J Cell Physiol 194:1–12

    Article  CAS  Google Scholar 

  23. Weir GC, Bonner-Weir S (2004) Five stages of evolving β-cell dysfunction during progression to diabetes. Diabetes 53:S16–S21

    CAS  Google Scholar 

  24. Quddusi S, Vahl TP, Hanson K, Prigeon RL, D’Alessio DA (2003) Differential effects of acute and extended infusions of glucagon-like peptide-1 on first- and second-phase insulin secretion in diabetic and nondiabetic humans. Diabetes Care 26:791–798

    CAS  Google Scholar 

  25. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF (1987) Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 84:3434–3438

    Article  CAS  Google Scholar 

  26. Jhala US, Canettieri G, Screaton RA, Kulkarni RN, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M (2003) cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev 17:1575–1580

    Article  CAS  Google Scholar 

  27. Liu D, Zhen W, Yang Z, Carter JD, Si H, Reynolds KA (2006) Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 55:1043–1050

    Article  CAS  Google Scholar 

  28. Vedavanam K, Srijayanta S, O’Reilly J, Raman A, Wiseman H (1999) Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE). Phytother Res 13:601–608

    Article  CAS  Google Scholar 

  29. White MF (1998) The IRS-signaling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182:3–11

    Article  CAS  Google Scholar 

  30. Kulkarni RN, Jhala US, Winnay JN, Krajewski S, Montminy M, Kahn CR (2004) PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 114:828–836

    Article  CAS  Google Scholar 

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Acknowledgment

This work was supported by a grant from the Korea Science and Engineering Foundation in Korea (M10510120001-05N1012-00111).

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Authors and Affiliations

  1. Food Functional Research Division, Korean Food Research Institutes, Seoul, Korea

    Dae Young Kwon

  2. Dept. of Food and Nutrition, Institute of Basic Sciences, Hoseo University, 165 Sechul-Ri Baebang-Myun Asan-Si, Chungnam-Do, 336-795, Korea

    Jin Sun Jang, Sang Mee Hong, Ji Eun Lee, So Ra Sung, Hye Ryeo Park & Sunmin Park PhD

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  1. Dae Young Kwon
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  2. Jin Sun Jang
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Correspondence to Sunmin Park PhD.

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Kwon, D.Y., Jang, J.S., Hong, S.M. et al. Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats. Eur J Nutr 46, 44–52 (2007). https://doi.org/10.1007/s00394-006-0630-y

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