Skip to main content
Log in

Effects of dietary active soybean trypsin inhibitors on pancreatic weights, histology and expression of STAT3 and receptors for androgen and estrogen in different tissues of rats

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Our previous study showed that soy milks could contain high levels of active soybean trypsin inhibitors (SBTI) if they were not properly processed. This study investigated the effects of consuming active SBTI on pancreatic weights, histology, trypsinogen production and expression of STAT3, receptors for androgen (AR) and estrogen (ER) in pancreas, liver and uterus of rats. Weanling Sprague–Dawley rats were randomly divided into 3 groups (8 females and 8 males/group) and fed diets containing either 20% casein protein (Casein) or 20% soy protein (SP) in the presence of high (1.42 BAEE unit/µg, SP + SBTI) or low (0.2 BAEE unit/µg, SP-SBTI) levels of active SBTI for 8 weeks. Ingestion of SP + SBTI diet markedly increased pancreatic weights and trypsinogen content (p < 0.01), and caused acinar cell hypertrophy, and reduced pancreatic STAT3, p-STAT3, AR and ERβ content, and increased uterine ERα and ERβ compared to the Casein or SP-SBTI diets (p < 0.05). The two SP-containing diets lowered hepatic STAT3, p-STAT3, and pancreatic ERα, and increased hepatic ERα and ERβ content in the female rats compared to the Casein diet (p < 0.05). This study demonstrated for the first time that consumption of high level of active SBTI not only increased pancreatic weights and acinar cell secretions, but also attenuated the expression of pancreatic STAT3, p-STAT3, AR, and ERβ proteins in both sexes and increased uterine ERα and ERβ content, and that dietary soy protein affected hepatic STAT3, p-STAT3, ERα and ERβ in a gender-dependent manner.

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
Fig. 3

Similar content being viewed by others

Abbreviations

AR:

Androgen receptor

BBI:

Bowman-Birk inhibitors

ER:

Estrogen receptor

KTI:

Kunitz trypsin inhibitor

SBTI:

Soybean trypsin inhibitor

SP:

Soy protein

STAT3:

Signal transducer and activator of transcription 3

p-STAT3:

Phosphorylated STAT3

References

  1. Bacon JR, Wanigatunga SCDR, An J, Fenwick GR (1995) A microassay for the analysis of trypsin inhibitor activity in peas. Food Chem 52:77–80

    Article  CAS  Google Scholar 

  2. Xu Z, Chen Y, Zhang C, Kong X, Hua Y (2012) The heat-induced protein aggregate correlated with trypsin inhibitor inactivation in soymilk processing. J Agric Food Chem 60:8012–8019

    Article  CAS  Google Scholar 

  3. Xiao CW, Wood CM, Robertson P, Gilani GS (2012) Protease inhibitor activities and isoflavone content in commercial soymilks and soy-based infant formulas sold in Ottawa, Canada. J Food Comp Anal 25:130–136

    Article  CAS  Google Scholar 

  4. Logsdon CD, Ji B (2013) The role of protein synthesis and digestive enzymes in acinar cell injury. Nat Rev Gastroenterol Hepatol 10:362–370

    Article  CAS  Google Scholar 

  5. Yuan S, Chang SK, Liu Z, Xu B (2008) Elimination of trypsin inhibitor activity and beany flavor in soy milk by consecutive blanching and ultrahigh-temperature (UHT) processing. J Agric Food Chem 56:7957–7963

    Article  CAS  Google Scholar 

  6. Temler RS, Dormond CA, Simon E, Morel B (1984) The effect of feeding soybean trypsin inhibitor and repeated injections of cholecystokinin on rat pancreas. J Nutr 114:1083–1091

    Article  CAS  Google Scholar 

  7. McGuinness EE, Morgan RG, Wormsley KG (1984) Effects of soybean flour on the pancreas of rats. Environ Health Perspect 56:205–212

    Article  CAS  Google Scholar 

  8. Cheftel JC, Cuq JL, Lorient D (1985) Amino acids, peptides, and proteins. In: Fennema OR (ed) Food chemistry. Marcel Dekker Inc, New York

    Google Scholar 

  9. Kostromina E, Gustavsson N, Wang X, Lim CY, Radda GK, Li C, Han W (2010) Glucose intolerance and impaired insulin secretion in pancreas-specific signal transducer and activator of transcription-3 knockout mice are associated with microvascular alterations in the pancreas. Endocrinology 151:2050–2059

    Article  CAS  Google Scholar 

  10. Xu W, Morford J, Mauvais-Jarvis F (2019) Emerging role of testosterone in pancreatic ß-cell function and insulin secretion. J Endocrinol. https://doi.org/10.1530/JOE-18-0573

    Article  PubMed  PubMed Central  Google Scholar 

  11. Navarro G, Xu W, Jacobson DA, Wicksteed B, Allard C, Zhang G, De GK, Kim SH, Wu H, Zhang H, Verhoeven G, Katzenellenbogen JA, Mauvais-Jarvis F (2016) Extranuclear actions of the androgen receptor enhance glucose-stimulated insulin secretion in the male. Cell Metab 23:837–851

    Article  CAS  Google Scholar 

  12. Mishra JS, More AS, Kumar S (2018) Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats. Biol Reprod 98:520–531

    Article  Google Scholar 

  13. Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquie M, Gauthier BR, Nef S, Stefani E, Nadal A (2008) Pancreatic insulin content regulation by the estrogen receptor ER alpha. PLoS One 3:e2069

    Article  Google Scholar 

  14. Alonso-Magdalena P, Ropero AB, Garcia-Arevalo M, Soriano S, Quesada I, Muhammed SJ, Salehi A, Gustafsson JA, Nadal A (2013) Antidiabetic actions of an estrogen receptor beta selective agonist. Diabetes 62:2015–2025

    Article  CAS  Google Scholar 

  15. Soriano S, Ropero AB, Alonso-Magdalena P, Ripoll C, Quesada I, Gassner B, Kuhn M, Gustafsson JA, Nadal A (2009) Rapid regulation of K(ATP) channel activity by 17ß-estradiol in pancreatic ß-cells involves the estrogen receptor ß and the atrial natriuretic peptide receptor. Mol Endocrinol 23:1973–1982

    Article  CAS  Google Scholar 

  16. Vogel H, Mirhashemi F, Liehl B, Taugner F, Kluth O, Kluge R, Joost HG, Schurmann A (2013) Estrogen deficiency aggravates insulin resistance and induces beta-cell loss and diabetes in female New Zealand obese mice. Horm Metab Res 45:430–435

    Article  CAS  Google Scholar 

  17. Chen Q, Wood C, Gagnon C, Cober ER, Frégeau-Reid JA, Gleddie S, Xiao CW (2014) The alpha’ subunit of beta-conglycinin and the A1–5 subunits of glycinin are not essential for many hypolipidemic actions of dietary soy proteins in rats. Eur J Nutr 53:1195–1207

    Article  CAS  Google Scholar 

  18. AACC (1999) AACC International Method 22-40.01: Measurement of trypsin inhibitor activity of soy products-spectrophotometric method. Approved Methods of Analysis, 11th ed

  19. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951

    Article  CAS  Google Scholar 

  20. Crass RA, Morgan RG (1982) The effect of long-term feeding of soya-bean flour diets on pancreatic growth in the rat. Br J Nutr 47:119–129

    Article  CAS  Google Scholar 

  21. Nitsan Z, Nir I, Liener IE (1983) Accentuated response to raw soya-bean meal by meal feeding. Arch Toxicol Suppl 6:177–181

    Article  CAS  Google Scholar 

  22. Cheranov SY, Karpurapu M, Wang D, Zhang B, Venema RC, Rao GN (2008) An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis. Blood 111:5581–5591

    Article  CAS  Google Scholar 

  23. Harada N, Yoda Y, Yotsumoto Y, Masuda T, Takahashi Y, Katsuki T, Kai K, Shiraki N, Inui H, Yamaji R (2018) Androgen signaling expands beta-cell mass in male rats and beta-cell androgen receptor is degraded under high-glucose conditions. Am J Physiol Endocrinol Metab 314:E274–E286

    Article  Google Scholar 

  24. Tiano JP, Delghingaro-Augusto V, Le MC, Liu S, Kaw MK, Khuder SS, Latour MG, Bhatt SA, Korach KS, Najjar SM, Prentki M, Mauvais-Jarvis F (2011) Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents beta cell failure in rodent models of type 2 diabetes. J Clin Invest 121:3331–3342

    Article  CAS  Google Scholar 

  25. Coldham NG, Sauer MJ (2000) Pharmacokinetics of [(14)C]Genistein in the rat: gender-related differences, potential mechanisms of biological action, and implications for human health. Toxicol Appl Pharmacol 164:206–215

    Article  CAS  Google Scholar 

  26. Xiao CW (2008) Health effects of soy protein and isoflavones in humans. J Nutr 138:1244S-1249S

    Article  CAS  Google Scholar 

  27. Thompson C, Lucier GW (1983) Hepatic estrogen responsiveness. Possible mechanisms for sexual dimorphism. Mol Pharmacol 24:69–76

    CAS  PubMed  Google Scholar 

  28. Yamamoto T, Matsuda T, Junicho A, Kishi H, Saatcioglu F, Muraguchi A (2000) Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling. FEBS Lett 486:143–148

    Article  CAS  Google Scholar 

  29. Xiao CW, Wood CM, Weber D, Aziz SA, Mehta R, Griffin P, Cockell KA (2014) Dietary supplementation with soy isoflavones or replacement with soy proteins prevents hepatic lipid droplet accumulation and alters expression of genes involved in lipid metabolism in rats. Genes Nutr 9:373

    Article  CAS  Google Scholar 

  30. Chatterjee C, Liu J, Wood C, Gagnon C, Cober ER, Fregeau-Reid JA, Gleddie S, Xiao CW (2018) The alpha’ subunit of beta-conglycinin and various glycinin subunits of soy are not required to modulate hepatic lipid metabolism in rats. Eur J Nutr 57:1157–1168

    Article  CAS  Google Scholar 

  31. Notides AC, Hamilton DE, Rudolph JH (1973) The action of a human uterine protease on the estrogen receptor. Endocrinology 93:210–216

    Article  CAS  Google Scholar 

  32. Tilzer LL, McFarland RT, Plapp FV, Evans JP, Chiga M (1981) Different ionic forms of estrogen receptor in rat uterus and human breast carcinoma. Cancer Res 41:1058–1063

    CAS  PubMed  Google Scholar 

  33. Billings PC, St Clair WH, Maki PA, Kennedy AR (1992) Distribution of the Bowman Birk protease inhibitor in mice following oral administration. Cancer Lett 62:191–197

    Article  CAS  Google Scholar 

  34. Finlay TH, Katz J, Rasums A, Seiler S, Levitz M (1981) Estrogen-stimulated uptake of alpha 1-protease inhibitor and other plasma proteins by the mouse uterus. Endocrinology 108:2129–2136

    Article  CAS  Google Scholar 

  35. Figarella C, Negri GA, Guy O (1974) Studies on inhibition of the two human trypsins. In: Fritz H, Tschesche H, Greene LJ (eds) Proteinase inhibitors. Proceedings of the 2nd International Research Conference. Springer, Berlin/Heidelberg/New York

  36. Mallory PA, Travis J (1975) Inhibition spectra of the human pancreatic endopeptidases. Am J Clin Nutr 28:823–830

    Article  CAS  Google Scholar 

  37. Guerrero-Beltran JA, Estrada-Giron Y, Swanson BG, Barbosa-Canovas GV (2009) Pressure and temperature combination for inactivation of soymilk trypsin inhibitors. Food Chem 116:676–679

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Stephen Gleddie at Agriculture and Agri-Food Canada for providing soy proteins. We thank the technicians in the Scientific Service Division, Food Directorate, Health Canada for their assistance during the animal experimentation phase.

Funding

This research was supported by Health Canada.

Author information

Authors and Affiliations

Authors

Contributions

CWX designed the animal study and conducted data analysis and prepared the manuscript. CW coordidated the animal study and conducted sample analysis. LAC, ML, and MR analysed the samples and participated in manuscript preparation.

Corresponding author

Correspondence to Chao-Wu Xiao.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Informed consent

All authors in this paper have read the final manuscript and approved for publication.

Animal rights

The animal experimental protocol was approved by the Health Canada-Ottawa Animal Care Committee, and all animal handling and care followed the guidelines of the Canadian Council for Animal Care.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 38643 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, CW., Wood, C., Cunningham, L.A. et al. Effects of dietary active soybean trypsin inhibitors on pancreatic weights, histology and expression of STAT3 and receptors for androgen and estrogen in different tissues of rats. Mol Biol Rep 48, 4591–4600 (2021). https://doi.org/10.1007/s11033-021-06491-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06491-x

Keywords

Navigation