Development of Insulin Resistance after Long‐Term Glucocorticoid Action as the Mechanism of Transformation of Gastroprotective Effect Glucocorticoids into Proulcerogenic Consequences

Abstract

Our previous findings suggest that an initial action of endogenous glucocorticoids, including stress‐produced ones, as well as exogenous glucocorticoids, even used at pharmacological doses, is physiological gastroprotective. Prolongation of the hormonal action, even after single glucocorticoid injection, may lead to transformation of gastroprotective hormonal effect to proulcerogenic one. Single injection of dexamethasone or cortisol, but not corticosterone, resulted in transformation of initially gastroprotective hormonal action to proulcerogenic one. Glucocorticoid‐induced long‐term maintenance of blood glucose level accompanied with catabolic effects as well as glucocorticoid‐induced blood corticosterone deficiency in rats may be the reasons of the transformation of gastroprotective action of glucocorticoids to their proulcerogenic effect. The present study was design for further understanding of the mechanisms of transformation of initially gastroprotective action of glucocorticoids to proulcerogenic effect. In experiments in rats we verified the hypothesis that a development of insulin resistance after prolongation of glucocorticoid action may be one of the mechanisms of such transformation. For this, the effects of dexamethasone, cortisol and corticosterone (at pharmacological doses) on insulin sensitivity were investigated at different time points after their single administration. Insulin sensitivity was expressed as a percentage of blood glucose reduction comparatively to its baseline levels. Insulin was injected at a dose 2 IU/kg (i.p.). Blood glucose levels were determined before and 1.5 hours after insulin injection. Prolongation of dexamethasone or cortisol action resulted in a decrease in insulin sensitivity (development of insulin resistance) at the time points when their proulcerogenic effect appeared. However, the sensitivity to insulin was not changed comparing with appropriate controls at those time points when the gastroprotective effect of glucocorticoids appeared. Moreover, prolongation of corticosterone action did not lead either to the transformation of its gastroprotective effect to proulcerogenic one, or to the appearance of insulin resistance. The data obtained suggest that the development of insulin resistance after prolongation glucocorticoid action is one of the mechanisms of transformation of their gastroprotective action into proulcerogenic consequences.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) №14‐15‐00790.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.