Fat feeding produces whole-body insulin resistance and decreased glucose uptake in muscle tissue of rats. To examine the effect of glucocorticoid blockade on the insulin resistance caused by high-fat feeding, four groups of rats were fed diets high in starch (70% of calories) or fat (59% of calories) for 4 weeks with or without the antiglucocorticoid RU486 (69.8 μmol · kg−1 · day−1) in the food. Whole-body insulin action was assessed by the euglycemic clamp technique at an upper physiological insulin level with bolus 2-[3H]deoxyglucose to determine individual tissue insulin-stimulated glucose uptake. Whole-body glucose utilization (clamp glucose infusion rate [GIR]) was decreased by high-fat feeding (GIR 68.3 ± 12.2 vs. 182.6 ± 12.8 μmol · kg−1 · min−1 for the starch-fed group; P < 0.001). Addition of RU486 to the diet significantly improved (GIR 133.9 ± 12.8 μmol · kg−1 · min−1; P < 0.01), but did not fully reverse, the insulin resistance caused by fat feeding. RU486 was without effect in the starch-fed rats. In skeletal muscles, RU486 ameliorated 62 and 68% of the insulin resistance produced by fat feeding in red quadriceps and extensor digitorum longus hindlimb muscles, respectively, but had no effect in heart or white adipose tissue. These results suggest that glucocorticoids play, in a tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by high-fat feeding.
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June 01 1995
Amelioration of High-Fat Feeding–Induced Insulin Resistance in Skeletal Muscle With the Antiglucocorticoid RU486 Free
Masataka Kusunoki;
Masataka Kusunoki
Department of Internal Medicine, Aichi Medical University
Nagoya, Japan
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Gregory J Cooney;
Gregory J Cooney
Department of Endocrinology, Royal Prince Alfred Hospital
Camperdown
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Tsutomu Hara;
Tsutomu Hara
Department of Endocrinology, Royal Prince Alfred Hospital
Camperdown
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Leonard H Storlien
Leonard H Storlien
Department of Endocrinology, Royal Prince Alfred Hospital
Camperdown
Department of Biomedical Science, University of Wollongong
Wollongong, New South Wales, Australia
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Address correspondence and reprint requests to Prof. Leonard H. Storlien, Department of Biomedical Science, University of Wollongong, Northfield Ave., Wollongong, NSW 2522, Australia.
1
GIR, glucose infusion rate.
Diabetes 1995;44(6):718–720
Article history
Received:
January 10 1995
Revision Received:
March 23 1995
Accepted:
March 23 1995
PubMed:
7789638
Citation
Masataka Kusunoki, Gregory J Cooney, Tsutomu Hara, Leonard H Storlien; Amelioration of High-Fat Feeding–Induced Insulin Resistance in Skeletal Muscle With the Antiglucocorticoid RU486. Diabetes 1 June 1995; 44 (6): 718–720. https://doi.org/10.2337/diab.44.6.718
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