Evolution of dexamethasone-induced insulin resistance in rats.
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 micrograms.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 less than 0.05) and 48-h (198 +/- 21, P less than 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 less than 0.09; 1,732 +/- 197, P less than 0.005; 1,567 +/- 107, P less than 0.001 in 6-, 48-, and 96-h treated rats, respectively, compared with 937 +/- 99 mU.l-1 x 55 min-1 in control rats). The metabolic clearance rate of glucose was higher in the dexamethasone-treated rats (200 +/- 14, P less than 0.07; 227 +/- 18, P less than 0.01; 227 +/- 17, P less than 0.01 in 6-, 48-, and 96-h groups, respectively, compared with 165 +/- 10 ml/55 min in control rats).(ABSTRACT TRUNCATED AT 250 WORDS)
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
L
L
Stojanovska
G
G
Rosella
J
J
Proietto
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011773:Pyruvates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D003907:Dexamethasone; D005947:Glucose