Peripheral insulin sensitivity is decreased by elevated non-esterified fatty acid level in dexamethasone-treated rats.
The pathogenesis of glucocorticoid-induced insulin resistance in the peripheral tissue was studied by perfusion experiments of the isolated rat hindquarter and insulin tolerance tests in the rat with the cutting off operation of blood supplies to the liver, kidneys, intestines and pancreas. The rat was injected with 0.5 mg/kg dexamethasone for 7 days. Just after the multiple functional organectomies, insulin was loaded in doses of 0.1 and 0.5 U/kg. Plasma insulin levels during 0-10 min were approximately 100-20 and 500-100 microU/ml, respectively. The decreasing rates in plasma glucose level after injections of saline and 0.1 U/kg insulin were much smaller in dexamethasone-treated than control rats (0.0+/-7.2 vs 13.3+/-3.4%/10 min, p<0.05, and 8.0+/-5.8 vs 39.4+/-3.7%/10 min, p<0.01 respectively). The decreasing rate after 0.5 U/kg insulin loads was similar between both groups (40.2+/-10.0 in dexamethasone-treated and 52.3+/-7.3%/10 min in control rats). Plasma non-esterified fatty acids were raised in dexamethasone-treated compared to control rats (1.23+/-0.23 vs 0.73+/-0.08 mM, p<0.01). In the hindquarter perfusion study, glucose uptake in the dexamethasone-treated rat leg was no less than in the normal rat leg under a palmitate-free condition, and was decreased by the addition of 1.0 mM palmitate without and together with 100 and 500 microU/ml insulin. These results suggest that the glucocorticoid-induced peripheral insulin resistance is characterised by the decreased sensitivity and the preserved responsiveness to insulin, and is caused mainly by an elevated non-esterified fatty acid level.
Mokuda
O
O
Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara, Japan.
Sakamoto
Y
Y
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005934:Glucagon / Q000097:blood; D005938:Glucocorticoids / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D019308:Palmitic Acid; D003907:Dexamethasone; D005934:Glucagon