Skip to main content
SpringerLink
Log in

Deleterious Effects of Supplementation with Dehydroepiandrosterone Sulphate or Dexamethasone on Rat Insulin-Secreting Cells Under In Vitro Culture Condition

  • Published:
Bioscience Reports

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Dehydroepiandrosterone (DHEA) and glucocorticoids are steroid hormones synthesised in the adrenal cortex. Administration of DHEA, its sulphate derivative, DHEAS, and more controversially dexamethasone (DEX), a synthetic glucocorticoid, have beneficial effects in diabetic animals. Cultivating BRIN-BD11 cells for 3 days with either DHEAS (30 μM) or DEX (100 nM), reduced total cell number and reduced cell viability and cellular insulin content. DHEAS-treated cells had poor glucose responsiveness and regulated insulin release, coupled with reduced basal insulin release. In contrast, DEX-treated cells lacked responsiveness to glucose and membrane depolarisation, and both protein kinase A (PKA) and protein kinase C (PKC) secretory pathways were desensitised. Therefore, we conclude that this steroid hormone and synthetic glucocorticoid are not beneficial to pancreatic β-cells in vitro.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

DHEAS:

Dehydroepiandrosterone sulphate

DEX:

Dexamethasone

FBS:

Foetal bovine serum

References

  • Akiyama T, Takasawa S, Nata K, Kobayashi S, Abe M, Shervani NJ, Ikeda T, Nakagawa K, Unno M, Matsuno S, Okamoto H (2001) Activation of Reg gene, a gene for insulin-producing beta-cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation. Proc Natl Acad Sci USA 98:48–53

    Article  PubMed  CAS  Google Scholar 

  • Aksoy Y, Yapanoglu T, Aksou H, Yildirim AK (2004) The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced oxidative stress in rabbits. Urol Res 32:93–96

    Article  PubMed  CAS  Google Scholar 

  • Atouf F, Tazi A, Polak M, Czernichow P, Scharfmann R (1995) Dexamethasone regulates the expression of neuronal properties of a rat insulinoma cell line. J Neuroendocrinol 7:957–964

    Article  PubMed  CAS  Google Scholar 

  • Bone AJ, Banister SH, Zhang S (1994) Islet cell defence and repair mechanisms in insulin-dependent diabetes: a role for the pancreatic regenerating (Reg) gene? Biochem Soc Trans 22:37–41

    PubMed  CAS  Google Scholar 

  • Bone AJ, Banister SH, Zhang S (1997) The REG gene and islet cell repair and renewal in type 1 diabetes. In: Soria B (ed) Physiology and pathophysiology of the islets of Langerhans. Plenum Press, New York, pp 321–327

    Google Scholar 

  • Cetkovic-Cvrlje M, Sandler S, Eizirik DL (1993) Nicotinamide and dexamethasone inhibit interleukin-1-induced nitric oxide production by RINm5F cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase. Endocrinology 133:1739–1743

    Article  PubMed  CAS  Google Scholar 

  • Coleman DL (1995) Hypoglycaemic action of the aetiocholanolones in mice. In: Flatt PR, Ioannides C (eds) Drugs, diet, and disease. Ellis Horwood Limited, Hertfordshire, UK, pp 201–231

    Google Scholar 

  • Coleman DL, Leiter EH, Schwizer RW (1982) Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes 31:830–833

    Article  PubMed  CAS  Google Scholar 

  • Coleman DL, Leiter EH, Applezweig N (1984a) Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db). Endocrinology 115:239–243

    Article  CAS  Google Scholar 

  • Coleman DL, Schwizer RW, Leiter EH (1984b) Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice. Diabetes 33:26–32

    Article  CAS  Google Scholar 

  • Couce M, Kane LA, O’Brien TD, Charlesworth J, Soeller W, McNeish J, Kreutter D, Roche P, Butler PC (1996) Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and beta-cell dysfunction. Diabetes 45:1094–1101

    Article  PubMed  CAS  Google Scholar 

  • Dillon JS, Yaney GC, Zhou Y, Voilley N, Bowen S, Chipkin S, Bliss CR, Schultz V, Schuit FC, Prentki M, Waxman DJ, Corkey BE (2000) Dehydroepiandrosterone sulfate and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta-cells. Diabetes 49:2012–2020

    Article  PubMed  CAS  Google Scholar 

  • Flatt PR, Bailey CJ (1981) Abnormal plasma glucose and insulin responses in heterozygous(ob/+) mice. Diabetologia 20:573–577

    Article  PubMed  CAS  Google Scholar 

  • Francis PJ, Southgate JL, Wilkin TJ, Bone AJ (1992) Expression of an islet regenerating (reg) gene in isolated rat islets: effects of nutrient and non-nutrient growth factors. Diabetologia 35:238–242

    Article  PubMed  CAS  Google Scholar 

  • Giddings SJ, Orland MJ, Weir GC, Bonner Weir S, Permutt MA (1985) Impaired insulin biosynthetic capacity in a rat model for non-insulin-dependent diabetes. Studies with dexamethasone. Diabetes 34:235–240

    Article  PubMed  CAS  Google Scholar 

  • Giroix MH, Malaisse-Lagae F, Portha B, Sener A, Malaisse WJ (1997) Effects of dehydroepiandrosterone in rats injected with streptozotocin during the neonatal period. Biochem Mol Med 61:72–81

    Article  PubMed  CAS  Google Scholar 

  • Hunt SM, Chraznowska C, Barnett CR, Brand HN, Fawell JK (1987) A comparison of in vitro cytotoxicity assays and their application to water samples. Altern Lab Anim 15:20–29

    CAS  Google Scholar 

  • Iwasaki Y, Asai M, Yoshida M, Nigawara T, Kambayashi M, Nakashima N (2004) Dehydroepiandrosterone-sulfate inhibits nuclear factor-kappaB-dependent transcription in hepatocytes, possibly through antioxidant effect. J Clin Endocrinol Metab 89:3449–3454

    Article  PubMed  CAS  Google Scholar 

  • Korsgren O, Andersson A, Sandler S. (1993) In vitro screening of putative compounds inducing fetal porcine pancreatic beta-cell differentiation: implications for cell transplantation in insulin-dependent diabetes mellitus. Ups J Med Sci 98:39–52

    Article  PubMed  CAS  Google Scholar 

  • Laychock SG (1998) Rat pancreatic islet and RINm5F cell responses to epiandrosterone, dehydroepiandrosterone and interleukin-1 beta. Biochem Pharmacol 55:1453–1464

    Article  PubMed  CAS  Google Scholar 

  • Laychock SG, Bauer AL (1996) Epiandrosterone and dehydroepiandrosterone affect glucose oxidation and interleukin-1 beta effects in pancreatic islets. Endocrinology 137:3375–3385

    Article  PubMed  CAS  Google Scholar 

  • Lenzen S, Bailey CJ (1984) Thyroid hormones, gonadal and adrenocortical steroids and the function of the islets of Langerhans. Endocr Rev 5:411–434

    Article  PubMed  CAS  Google Scholar 

  • McClenaghan NH, Barnett CR, Ah Sing E, Abdel Wahab YHA, O’Harte FPM, Yoon TW, Swanston Flatt SK, Flatt PR (1996) Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion. Diabetes 45:1132–1140

    Article  PubMed  CAS  Google Scholar 

  • Melvin WS, Boros LG, Muscarella P, Brandes JL, Johnson JA, Fisher WE, Schirmer WJ, Ellison EC (1997) Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo. Surgery 121:392–397

    Article  PubMed  CAS  Google Scholar 

  • Nawata H, Yanase T, Goto K, Okabe T, Ashida K (2002) Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Ageing Dev 123:1101–1106

    Article  PubMed  CAS  Google Scholar 

  • Neuberger TJ, Kalimi O, Regelson W, Kalimi M, De Vries GH (1994) Glucocorticoids enhance the potency of Schwann cell mitogens. J Neurosci Res 38:300–313

    Article  PubMed  CAS  Google Scholar 

  • Ogawa A, Johnson JH, Ohneda M, McAllister CT, Inman L, Alam T, Unger RH (1992) Roles of insulin resistance and beta-cell dysfunction in dexamethasone-induced diabetes. J Clin Invest 90:497–504

    Article  PubMed  CAS  Google Scholar 

  • Ohneda M, Johnson JH, Inman LR, Unger RH (1993) GLUT-2 function in glucose-unresponsive beta cells of dexamethasone-induced diabetes in rats. J Clin Invest 92:1950–1956

    Article  PubMed  CAS  Google Scholar 

  • Salek FS, Bigos KL, Kroboth PD (2002) The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies. J Clin Pharmacol 42:247–266

    Article  PubMed  CAS  Google Scholar 

  • Sandler S, Andersson A (1982) Short- and long-term effects of dimethyl sulfoxide on mouse pancreatic islet B-cell function in vitro. Cryobiology 19:299–305

    Article  PubMed  CAS  Google Scholar 

  • Shinozuka Y, Okada M, Oki T, Sagane K, Mizui Y, Tanaka I, Katayama K, Murakami-Murofushi K (2001) Altered expression of HES-1, BETA2/NeuroD, and PDX-1 is involved in impaired insulin synthesis induced by glucocorticoids in HIT-T15 cells. Biochem Biophys Res Commun 287:229–235

    Article  PubMed  CAS  Google Scholar 

  • Weinhaus AJ, Bhagroo NV, Brelje TC, Sorenson RL (2000) Dexamethasone counteracts the effect of prolactin on islet function: implications for islet regulation in late pregnancy. Endocrinology 141:1384–1393

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

These studies were supported by University of Ulster Strategy Funding and an Overseas Research Studentship awarded to Hui-Kang Liu of the committee of Vice Chancellor and Principals.

Author information

Authors and Affiliations

  1. School of Biomedical Sciences, University of Ulster, BT52 1SA, Coleraine, N. Ireland, UK

    Hui-Kang Liu, Brian D. Green, Neville H. McClenaghan, Jannie T. McCluskey & Peter R. Flatt

Authors
  1. Hui-Kang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian D. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neville H. McClenaghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jannie T. McCluskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter R. Flatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter R. Flatt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, HK., Green, B.D., McClenaghan, N.H. et al. Deleterious Effects of Supplementation with Dehydroepiandrosterone Sulphate or Dexamethasone on Rat Insulin-Secreting Cells Under In Vitro Culture Condition. Biosci Rep 26, 31–38 (2006). https://doi.org/10.1007/s10540-006-9001-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10540-006-9001-4

Keywords

Search

Navigation