This work continues our studies of the mechanisms of transformation of the initial gastroprotective action of glucocorticoid hormones into a proulcerogenic action. Experiments on rats tested the suggestion that the development of insulin resistance after prolonged exposure to glucocorticoid hormones may be one of the mechanisms of this transformation. This was addressed by studying the effects of dexamethasone, corticosterone, and hydrocortisone on insulin sensitivity at different time points after single doses of pharmacological size. Insulin sensitivity was evaluated in terms of the decrease in the blood glucose level 1.5 h after administration of insulin (2 IU/kg, i.p.). Decreases in glucose levels were expressed as percentages of baseline (pre-insulin) glucose levels. The results indicated that at those time points at which these hormone had previously been found to have gastroprotective actions, insulin sensitivity remained unaltered from that in control animals. Administration of dexamethasone and hydrocortisone after prolonged exposure led to decreases in insulin sensitivity at those time points at which their proulcerogenic effects had been seen. Increases in the duration of exposure to corticosterone did not produce any changes in insulin sensitivity or transformation of its gastroprotective effect into a proulcerogenic action. These data support the suggestion that the development of insulin resistance after prolonged exposure to glucocorticoid hormones can be regarded as one of the mechanisms of the transformation of their gastroprotective effects into proulcerogenic actions.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
O. Yu. Morozova, T. R. Bagaeva, and L. P. Filaretova, “Mechanisms of the proulcerogenic action of hydrocortisone given at a pharmacological dose on the gastric mucosa,” Ros. Fiziol. Zh., 102, No. 3, 330–339 (2016).
T. T. Podvigina and L. P. Filaretova, “The double effect of glucocorticoid hormones on the gastric mucosa,” Usp. Fiziol. Nauk., 45, No. 4, 19–33 (2014).
T. T. Podvigina, T. R. Bagaeva, P. Yu. Bobryshev, and L. P. Filaretova, “Increased sensitivity of the gastric mucosa to the ulcerogenic action of indomethacin in rights with diabetes,” Byull. Eksperim. Biol. Med., 152, No. 7, 48–52 (2011).
T. T. Podvigina, T. R. Bagaeva, O. Yu. Morozova, and L. P. Filaretova, “Comparative analysis of the effects of corticosterone, hydrocortisone, and dexamethasone on the formation of erosions in the stomach in rats,” Ros. Fiziol. Zh., 98, No. 7, 879–889 (2012).
A. A. Filaretov, “Patterns of functioning of the hypothalamo-hypophyseal-adrenocortical system,” Usp. Fiziol. Nauk., 24, No. 2, 70–83 (1993).
L. P. Filaretova, “The contribution of glucocorticoid hormones to gastroprotection,” Usp. Fiziol. Nauk., 45, No. 1, 43–55 (2014).
L. P. Filaretova, T. R. Bagaeva, O. Yu. Morozova, and T. T. Podvigina, “Transformation of the gastroprotective effects of glucocorticoid hormones into pathological ulcerogenic actions,” Ros. Fiziol. Zh., 96, No. 8, 806–816 (2010).
J. Burén, Y. C. Lai, M. Lundgren, et al., “Insulin action and signalling in fat and muscle from dexamethasone-treated rats,” Arch. Biochem. Biophys., 474, No. 1, 91–101 (2008).
R. A. DeFronzo, J. D. Tobin, and R. Andres, “Glucose clamp technique: a method for quantifying insulin secretion and resistance,” Am. J. Physiol., 237, No. 3, E214–E223 (1979).
G. Di Dalmazi, U. Pagotto, R. Pasquali, and V. Vicennati, “Glucocorticoids and type 2 diabetes: from physiology to pathology,” J. Nutr. Metab., 525093 (2012), publ. online, doi: https://doi.org/10.1155/2012/525093.
H. A. Ferris and C. R. Kahn, “New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it,” J. Clin. Invest., 122, No. 11, 3854–3857 (2012).
L. Filaretova, “Gastroprotective role of glucocorticoids during NSAID-induced gastropathy,” Curr. Pharm. Des., 19, No. 1, 29–33 (2013).
L. Filaretova, “Gastroprotective effect of stress preconditioning: involvement of glucocorticoids,” Curr. Pharm. Des., 23, No. 27, 3923–3927 (2017).
L. P. Filaretova, A. A. Filaretov, and G. B. Makara, “Corticosterone increase inhibits stress-induced gastric erosions in rats,” Am. J. Physiol., 274, No. 37, G1024–G1030 (1998).
L. Filaretova, T. Podvigina, T. Bagaeva, and G. Makara, “Gastroprotective action of glucocorticoids during the formation and the healing of indomethacin-induced gastric erosions in rats,” J. Physiol. Paris, 95, No. 1–6, 201–208 (2001).
L. Filaretova, T. Podvigina, T. Bagaeva, and O. Morozova, “From gastroprotective to ulcerogenic effects of glucocorticoids: role of long-term glucocorticoid action,” Current Pharmac. Design, 20, No. 7, 1045–1050 (2014).
M. E. Keller-Wood, J. Shinsako, L. C. Keil, and M. F. Dallman, “Insulin-induced hypoglycemia in conscious dogs. I. Dose-related pituitary and adrenal responses,” Endocrinology, 109, No. 3, 818–824 (1981).
O. Mokuda and Y. Sakamoto, “Peripheral insulin sensitivity is decreased by elevated nonesterifi ed fatty acid level in dexamethasone-treated rats,” Diabetes Nutr. Metab., 12, 252–255 (1999).
D. Qi, T. Pulinilkunnil, D. An, et al., “Single-dose dexamethasone induces whole-body insulin resistance and alters both cardiac fatty acid and carbohydrate metabolism,” Diabetes, 53, No. 7, 1790–1797 (2004).
R. M. Reynolds and B. R. Walker, “Human insulin resistance: the role of glucocorticoids,” Diabetes Obes. Metab., 5, No. 1, 5–12 (2003).
P. Schneiter and L. Tappy, “Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans,” Am. J. Physiol., 275, E806–Е813 (1998).
C. Severino, P. Brizzi, A. Solinas, et al., “Low-dose dexamethasone in the rat: a model to study insulin resistance,” Am. J. Physiol. Endocrinol. Metab., 283, No. 2, E367–Е373 (2002).
K.-H. Su, V. Chandramouli, F. Ismail-Beigi, and R. F. Muzic, “Dexamethasone-induced insulin resistance: Kinetic modeling using novel PET radiopharmaceutical 6-deoxy-6-[18F]fl uoro-D-glucose,” Mol. Imaging Biol., 16, No. 5, 710–720 (2014).
N. Venkatesan, J. Lim, C. Bouch, D. Marciano, and M. B. Davidson, “Dexamethasone-induced impairment in skeletal muscle glucose transport is not reversed by inhibition of free fatty acid oxidation,” Metabolism, 45, No. 1, 92–100 (1996).
S. P. Weinstein, T. Paquin, A. Pritsker, and R. S. Haber, “Glucocorticoid- induced insulin resistance: dexamethasone inhibits the activation of glucose transport in rat skeletal muscle by both insulin- and non-insulin-related stimuli,” Diabetes, 44, No. 4, 441–445 (1995).
M. Zarkovic, B. Beleslin, J. Ciric, et al., “Glucocorticoid effect on insulin sensitivity: a time frame,” J. Endocrinol. Invest., 31, No. 3, 238–242 (2008).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 104, No. 4, pp. 493–505, April, 2018.
Rights and permissions
About this article
Cite this article
Podvigina, T.T., Morozova, O.Y., Bagaeva, T.R. et al. Development of Insulin Resistance after Prolonged Exposure to Glucocorticoid Hormones as One of the Mechanisms of Transformation of Their Gastroprotective Effect into a Proulcerogenic Action. Neurosci Behav Physi 49, 979–986 (2019). https://doi.org/10.1007/s11055-019-00827-8
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-019-00827-8