Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Apr 15;212(1):135–141. doi: 10.1042/bj2120135

The effects of glucocorticoids on insulin-stimulated lipogenesis in primary cultures of rat hepatocytes.

J M Amatruda, S A Danahy, C L Chang
PMCID: PMC1152020  PMID: 6347191

Abstract

We used primary cultures of rat hepatocytes to evaluate the effects of glucocorticoids on insulin-responsive hepatic lipogenesis. The data indicate that hepatocytes incubated for 20 h with dexamethasone (0.1 microM) alone are profoundly resistant to the ability of insulin to stimulate lipogenesis acutely. In contrast, primary cultures of hepatocytes incubated with dexamethasone plus insulin are hyper-responsive to the ability of insulin to stimulate lipogenesis chronically. This potentiation of insulin action by a glucocorticoid occurs at physiological concentrations of the two hormones. Exposure to dexamethasone plus insulin for more than 4 h is required for the two hormones to enhance insulin action either by overcoming the insulin resistance induced by dexamethasone alone or by stimulating insulin action induced by insulin alone. Despite the marked potentiation of insulin action, hepatocytes exposed to dexamethasone plus insulin are less sensitive to insulin, as demonstrated by a shift to the right in the dose-response curve for insulin-stimulated lipogenesis. The resistance of hepatocytes to the acute effects of insulin after exposure to dexamethasone alone and the potentiation of insulin action and decreased sensitivity to insulin after exposure to insulin plus dexamethasone are all mediated by post-insulin-binding events. These studies demonstrate potentiation of insulin action in the liver by physiological concentrations of glucocorticoids and may have physiological significance for the regulation of normal hepatic lipogenesis, for the hyperlipidaemia observed with the pharmacological use of glucocorticoids, and for disease states in man associated with hyperinsulinaemia and hypercortisolism.

Full text

PDF
135

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALTMAN K. I., MILLER L. L., BLY C. G. The synergistic effect of cortisone and insulin on lipogenesis in the perfused rat liver as studied with alpha-C14-acetate. Arch Biochem Biophys. 1951 Apr;31(2):329–331. doi: 10.1016/0003-9861(51)90225-1. [DOI] [PubMed] [Google Scholar]
  2. Amatruda J. M., Newmeyer H. W., Chang C. L. Insulin-induced alterations in insulin binding and insulin action in primary cultures of rat hepatocytes. Diabetes. 1982 Feb;31(2):145–148. doi: 10.2337/diab.31.2.145. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Bagdade J. D., Yee E., Albers J., Pykalisto O. J. Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat. Metabolism. 1976 May;25(5):533–542. doi: 10.1016/0026-0495(76)90007-x. [DOI] [PubMed] [Google Scholar]
  5. Bagdade J., Casaretto A., Albers J. Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man. J Lab Clin Med. 1976 Jan;87(1):38–48. [PubMed] [Google Scholar]
  6. Berdanier C. D., Shubeck D. Interaction of glucocorticoid and insulin in the responses of rats to starvation-refeeding. J Nutr. 1979 Oct;109(10):1766–1771. doi: 10.1093/jn/109.10.1766. [DOI] [PubMed] [Google Scholar]
  7. Bouillon D. J., Berdanier C. D. Role of glucocorticoid in adaptive hyperlipogenesis in the rat. J Nutr. 1980 Feb;110(2):286–297. doi: 10.1093/jn/110.2.286. [DOI] [PubMed] [Google Scholar]
  8. Caro J. F., Amatruda J. M. Functional relationships between insulin binding, action, and degradation. A reassessment. J Biol Chem. 1980 Nov 10;255(21):10052–10055. [PubMed] [Google Scholar]
  9. Caro J. F., Amatruda J. M. Glucocorticoid-induced insulin resistance: the importance of postbinding events in the regulation of insulin binding, action, and degradation in freshly isolated and primary cultures of rat hepatocytes. J Clin Invest. 1982 Apr;69(4):866–875. doi: 10.1172/JCI110526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Caro J. F., Amatruda J. M. Insulin receptors in hepatocytes: postreceptor events mediate down regulation. Science. 1980 Nov 28;210(4473):1029–1031. doi: 10.1126/science.7001632. [DOI] [PubMed] [Google Scholar]
  11. Casaretto A., Marchioro T. L., Goldsmith R., Bagdade D. Hyperlipidaemia after successful renal transplantation. Lancet. 1974 Mar 23;1(7856):481–484. doi: 10.1016/s0140-6736(74)92787-1. [DOI] [PubMed] [Google Scholar]
  12. Cech J. M., Freeman R. B., Jr, Caro J. F., Amatruda J. M. Insulin action and binding in isolated hepatocytes from fasted, streptozotocin-diabetic, and older, spontaneously obese rats. Biochem J. 1980 Jun 15;188(3):839–845. doi: 10.1042/bj1880839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Czech M. P., Richardson D. K., Smith C. J. Biochemical basis of fat cell insulin resistance in obese rodents and man. Metabolism. 1977 Sep;26(9):1057–1078. doi: 10.1016/0026-0495(77)90024-5. [DOI] [PubMed] [Google Scholar]
  14. Diamant S., Shafrir E. Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids. Eur J Biochem. 1975 May 6;53(2):541–546. doi: 10.1111/j.1432-1033.1975.tb04097.x. [DOI] [PubMed] [Google Scholar]
  15. Kirk C. J., Verrinder T. R., Hems D. A. Fatty acid synthesis in the perfused liver of adrenalectomized rats. Biochem J. 1976 Jun 15;156(3):593–602. doi: 10.1042/bj1560593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Livingston J. N., Lockwood D. H. Effect of glucocorticoids on the glucose transport system of isolated fat cells. J Biol Chem. 1975 Nov 10;250(21):8353–8360. [PubMed] [Google Scholar]
  17. Olefsky J. M., Farquhar J. W., Reaven G. M. Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med. 1974 Oct;57(4):551–560. doi: 10.1016/0002-9343(74)90006-0. [DOI] [PubMed] [Google Scholar]
  18. Pykälistö O. J., Smith P. H., Brunzell J. D. Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity. J Clin Invest. 1975 Nov;56(5):1108–1117. doi: 10.1172/JCI108185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reaven E. P., Kolterman O. G., Reaven G. M. Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles. J Lipid Res. 1974 Jan;15(1):74–83. [PubMed] [Google Scholar]
  20. STEINBERG H., WEBB W. M., RAFSKY H. A. Hepatomegaly with fatty infiltration secondary to cortisone therapy: case report. Gastroenterology. 1952 Jun;21(2):304–309. [PubMed] [Google Scholar]
  21. Stern M. P., Kolterman O. G., Fries J. F., McDevitt H. O., Reaven G. M. Adrenocortical steroid treatment of rheumatic diseases. Effects on lipid metabolism. Arch Intern Med. 1973 Jul;132(1):97–101. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES