Skip to main content
SpringerLink
Log in

In vivo tissue specific modulation of rat insulin receptor gene expression in an experimental model of mineralocorticoid excess

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Insulin receptor (IR) gene expression at the mRNA level was investigated in hindlimb skeletal muscle, epididymal adipose tissue and in the liver of rats exposed to prolonged in vivo administration of deoxycorticosterone acetate (DOCA). Following treatment, plasma insulin levels were reduced while glucose levels increased compared to values in control rats. DOCA-treated animals showed an increase in blood pressure and a reduction in body weight. This treatment also induced hypokalemia and decreased plasma protein levels. Sodium levels were unaffected. Moreover, no differences in DNA and protein content or in the indicator of cell size (protein/DNA) were observed in the skeletal muscle or adipose tissue of animals. In contrast, there was a clear increase in the protein and DNA contents of the liver with no change in the indicator of cell size. Northern blot assays revealed 2 major IR mRNA species of approximately 9.5 and 7.5 Kb in the 3 tissues from control animals. DOCA treatment induced no change in the levels of either RNA species in skeletal muscle. However, a decrease of approximately 22% was detected in the levels of both species in adipose tissue whereas the liver showed an increase of 64%. These results provide the first evidence for an in vivo tissue-specific modulation of IR mRNA levels under experimental conditions of mineralocorticoid excess.

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

Similar content being viewed by others

References

  1. Funder JW: Aldosterone action. Annu Rev Physiol 55: 115-130, 1993

    Google Scholar 

  2. Rondinone C, Rodbard MD, Baker ME: Aldosterone stimulates differentiation of mouse 3T3-L1 cells into adipocytes. Endocrinology 132: 2421–2426, 1993

    Google Scholar 

  3. Sauer J, Castren M, Hopfner U, Holsboer F, Stalla GK, Arzt E: Inhibition of lipopolysaccharide-induced monocyte interleukin-1 receptor antagonist synthesis by cortisol: Involvement of the mineralocorticoid receptor. J Clin Endocrinol Metab 81: 73–79, 1996

    Google Scholar 

  4. Conn JW, Knope RF, Nesbit RM: Clinical characteristics of primary aldosteronism from an analysis of 145 cases. Am J Surg 107: 159–172, 1964

    Google Scholar 

  5. Conn JW: Hypertension, the potassium ion and impaired carbohydrate tolerance. New Engl J Med 273: 1135–1143, 1965

    Google Scholar 

  6. Gauda OP: Diabetes Secondary to endocrinopathies. In: H Rifkin, D Porte (eds). Ellenberg and Rifkin's Diabetes Mellitus: Theory and Practice. Elsevier, New York, 1990, pp 914–916

    Google Scholar 

  7. Carranza MC, Torres A, Calle C: Disminución en el numero y en la afinidad de los receptores de insulina en el tejido adiposo subcutáneo de un paciente con hiperaldosteronismo primario. Rev Clin Esp 188: 414–417, 1991

    Google Scholar 

  8. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM: The nuclear receptor superfamily: The second decade. Cell 83: 835–839, 1995

    Google Scholar 

  9. Funder JW: Glucocorticoid and mineralocorticoid receptors: Biology and clinical relevance. Annu Rev Med 48: 231–240, 1997

    Google Scholar 

  10. Leal MA, Cabañas C, Rius C, Aller P, Calle C: Modulation by dexamethasone of insulin binding and insulin receptor mRNA levels in U937 human promonocytic cells. Biochimie 74: 545–549, 1992

    Google Scholar 

  11. Leal MA, Aller P, Más A, Carranza MC, Calle C: Tissue-specific changes in insulin receptor mRNA concentrations in dexamethasonetreated and adrenalectomized rats. Endocr J 41: 737–741, 1994

    Google Scholar 

  12. Leal MA, Aller P, Torres A, Picardo A, Davila N, Calle C: Insulin receptor mRNA levels are modulated in a tissue-specific manner in Cushing's syndrome patients. Horm Metab Res 26: 349–350, 1994

    Google Scholar 

  13. Leal MA, Aller P, Calle C: Effect of dexamethasone on insulin receptor mRNA levels, RNA stability and isotype RNA pattern in U-937 human promonocytic cells. J Endocrinol Invest 19: 530–534, 1996

    Google Scholar 

  14. Papa V, Reese CC, Brunetti A, Vigneri R, Siiteri PK, Goldfine ID: Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinoma cells. Cancer Res 50: 7858–7862, 1990

    Google Scholar 

  15. Sesti G, Marini A, Briata P, Tullio AN, Montemurro A, Borboni P, De Pirro R, Gherzi R, Lauro R. Androgens increase insulin receptor mRNA levels, insulin binding, and insulin responsiveness in HEp-2 larynx carcinoma cells. Mol Cell Endocrinol 86: 111–118, 1992

    Google Scholar 

  16. Campión J, Aller P, Mata F, Davila N, Maestro B, Calle C: Regulation by aldosterone of insulin receptor mRNA levels in human promonocytic cells. Diabetologia 39 (Suppl I): A713, 1996

    Google Scholar 

  17. Navarro J, Sanchez A, Sáiz J, Ruilope LM, García-Estañ J, Romero JC, Moncada S, Lahera V: Hormonal, renal, and metabolic alterations during hypertension induced by chronic inhibition of NO in rats. Am J Physiol 267: R1516–R1512, 1994

    Google Scholar 

  18. Herbert V, Lau K-S, Gottlieb CW, Bleicher SJ: Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25: 1375–1384, 1965

    Google Scholar 

  19. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principe of protein-dye binding. Anal Biochemistry 72: 248–254, 1976

    Google Scholar 

  20. Labarca C, Paigen K: A simple, rapid and sensitive DNA assay procedure. Anal Biochem 102: 344–352, 1980

    Google Scholar 

  21. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159, 1987

    Google Scholar 

  22. Campión J, Aller P, Dávila N, Carranza MC, de Miguel R, Calle C: Tissue-specific modulation of insulin receptor mRNA levels in adrenaline-treated rats. Mol Cell Biochem 169: 165–169, 1997

    Google Scholar 

  23. Gomez-Sanchez EP, Venkataraman MT, Thwaites D, Fort C: ICV infusion of corticosterone antagonizes ICV-aldosterone hypertension. Am J Physiol 258: E649–E653, 1990

    Google Scholar 

  24. Dai S, Fraser H, McNeill JH: Effects of deoxycorticosterone acetate on glucose metabolism in nondiabetic and streptozotocin-diabetic rats. Can J Physiol Pharmacol 70: 1468–1472, 1992

    Google Scholar 

  25. Dai S, McNeill JH: Myocardial performance of STZ-diabetic DOCA-hypertensive rats. Am J Physiol 263: H1798–H1805, 1992

    Google Scholar 

  26. Spergel G, Schmidt P, Stern A, Bleicher SJ: Effects of hypokalemia on carbohydrate and lipid metabolism in the rat. Diabetes 16: 312–318, 1967

    Google Scholar 

  27. Ren P, de Feijter AW, Paul DL, Ruch RJ: Enhancement of liver cell gap junction protein expression by glucocorticoids. Carcinogenesis 15: 1807–1813, 1994

    Google Scholar 

  28. Goldstein BJ, Müller-Wieland D, Kahn CR: Variation in insulin receptor messenger ribonucleic acid expression in human and rodent tissues. Mol Endocrinol 1: 759–766, 1987

    Google Scholar 

  29. Knott RM, Hesketh JE, Trayhurn P. Insulin receptor gene expression in skeletal muscle and brown adipose tissue. Biochem Soc T 18: 1263, 1990

    Google Scholar 

  30. Tozzo E, Tessier F, Desbuquois B: Expression of the hepatic insulin receptor gene in the rat during postnatal development. Horm Metab Res 27: 163–168, 1995

    Google Scholar 

  31. Tewari M, Tewari DS, Taub R: Posttranscriptional mechanism account for differences in steady state levels of insulin receptor messenger RNA in different cells. Mol Endocrinol 5: 653–660, 1991

    Google Scholar 

  32. Brown RW, Diaz R, Robson AC, Kotelevtsev YV, Mullins JJ, Kaufman JH, Seckl JR: The ontogeny of 11 b-hydroxisteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology 137: 794–797, 1996

    Google Scholar 

  33. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM: Cloning of human mineralocorticoid receptor complementary DNA: Structural and functional kinship with the glucocorticoid receptor. Science 237: 268–275, 1987

    Google Scholar 

  34. Feldman D, Loose D: Glucocorticoid receptors in adipose tissue. Endocrinology 100: 398–405, 1977

    Google Scholar 

  35. Bloem LJ, Guo C, Pratt JH: Identification of a splice variant of the rat and human mineralocorticoid receptor genes. J Steroid Biochem Molec Biol 55: 159–162, 1995

    Google Scholar 

  36. Reul JM, Pearce PT, Funder JW, Krozowski ZS: Type I and type II corticosteroid receptor gene expression in the rat: Effect of adrenalectomy and dexamethasone administration. Mol Endocrinol 3: 1674–1680, 1989

    Google Scholar 

  37. Bamberger CM, Bamberger A-M, Wald M, Chrousos GP, Schulte HM: Inhibition of mineralocorticoid activity by the β-isoform of the human glucocorticoid receptor. J Steroid Biochem Biol 60: 43–50, 1997

    Google Scholar 

  38. Trapp T, Holsboer F: Heterodimerization between mineralocorticoid and glucocorticoid receptors increases the functional diversity of corticosteroid action. Trends Pharmacol Sci 17: 145–149, 1996

    Google Scholar 

  39. Ishimori M, Takeda N, Okumura S, Murai T, Inouye H, Yasuda K: Increased insulin sensitivity in patients with aldosterone producing adenoma. Clin Endocrinol 41: 433–438, 1994

    Google Scholar 

  40. Shimamoto K, Shiiki M, Ise T, Miyazaki Y, Higashiura K, Fukuoka M, Hirata A, Masuda A, Nakagawa M, Limura O: Does insulin resistance participate in an impaired glucose tolerance in primary aldosteronism? J Human Hypertens 8: 755–759, 1994

    Google Scholar 

  41. Lee J-K, Tsai SY: Multiple hormone response elements can confer glucocorticoid regulation on the human insulin receptor gene. Mol Endocrinol 8: 625–634, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Deptartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Spain

    Javier Campión, Begoña Maestro, María del Carmen Carranza & Consuelo Calle

  2. Deptartamento de Fisiología, Facultad de Medicina, Universidad Complutense, Spain

    Vicente Lahera & Victoria Cachofeiro

  3. Servicio de Endocrinología, Hospital C.P.H., Madrid, 4Spain

    Norma Dávila

Authors
  1. Javier Campión
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vicente Lahera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria Cachofeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Begoña Maestro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norma Dávila
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María del Carmen Carranza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Consuelo Calle
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Campión, J., Lahera, V., Cachofeiro, V. et al. In vivo tissue specific modulation of rat insulin receptor gene expression in an experimental model of mineralocorticoid excess. Mol Cell Biochem 185, 177–182 (1998). https://doi.org/10.1023/A:1006871309864

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006871309864

Search

Navigation