Evolution of dexamethasone-induced insulin resistance in rats

L. Stojanovska, G. Rosella, J. Proietto

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Glucocorticoids are known to cause insulin resistance and glucose intolerance. Although there have been many studies investigating the mechanism of this effect, several aspects remain to be clarified. The aim of this study was to investigate the evolution and sites of insulin resistance in dexamethasone-treated rats. To achieve this, chronically catheterized nonstressed rats had glucose kinetics measured during an oral glucose tolerance test by means of a double isotope technique. Studies were performed after 6, 48, or 96 h of dexamethasone administration (10 μg·rat-1·day-1) and were compared with control rats not treated with the steroid. Total hepatic glucose production (HGP) was increased in the 6-h (166 ± 8.3, P < 0.05) and 48-h (198 ± 21, P < 0.03) treated groups but not in the 96-h treated rats (140 ± 8, P = 0.99) compared with the controls (141 ± 8 mg/55 min). This increased HGP was despite the presence of higher insulin levels in the steroid-treated rats (1,220 ± 115, P < 0.09; 1,732 ± 197, P < 0.005; 1,567 ± 107, P < 0.001 in 6-, 48-, and 96-h treated rats, respectively, compared with 937 ± 99 mU·l-1·55 min-1 in control rats). The metabolic clearance rate of glucose was higher in the dexamethasone-treated rats (200 ± 14, P < 0.07; 227 ± 18, P < 0.01; 227 ± 17, P < 0.01 in 6-, 48-, and 96-h groups, respectively, compared with 165 ± 10 ml/55 min in control rats). It is concluded that, in rats, dexamethasone causes hepatic insulsin resistance with little measurable decrease in peripheral insulin action. The degree of hepatic insulin resistance decreases with longer duration of exposure to dexamethasone.

Original languageEnglish
Pages (from-to)E748-E756
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 21-5
Publication statusPublished - 1990
Externally publishedYes


  • corticosteroids
  • glucose kinetics
  • hepatic insulin resistance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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