Skeletal Muscle 11βHSD1 Activity of Nondiabetic Subjects is Unaltered in Central Obesity-associated Insulin Resistance

Abstract

Local activation of glucocorticoids in insulin target tissues by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) has been implicated in the etiology of the metabolic syndrome. In obesity, adipose tissue 11βHSD1 is upregulated, leading to the generation of higher tissue levels of cortisol, which may increase insulin resistance. However, skeletal muscle is the predominant site of insulin-mediated glucose disposal, which is known to be reduced in obesity. We aimed to determine if there is any relationship between skeletal muscle 11βHSD1 and markers of central adiposity and insulin resistance in nondiabetic subjects. 20 nondiabetic volunteers (8 males and 12 females, mean age 55±13 years, body mass index 21.5–47.6, mean 30.4±1.6 kg/m²) underwent a single fasting blood sample followed by a muscle biopsy of vastus lateralis under local anesthetic. Fasting glucose, insulin and adiponectin were measured in serum. Skeletal muscle 11βHSD1 oxoreductase activity was determined by measuring the conversion of radiolabelled ³H-cortisone to cortisol by thin layer chromatography. When subjects were categorised according to abdominal obesity (waist circumference ≥102 cm in men, ≥88 cm in women), there was no difference between the groups in skeletal muscle 11βHSD1 activity. There was no correlation between body mass index or waist circumference and 11βHSD1 activity or between HOMA and 11βHSD1 activity. Skeletal muscle 11βHSD1 oxoreductase activity is not altered in nondiabetic subjects with central obesity-associated insulin resistance. It is therefore unlikely that the in vivo insulin resistance observed in skeletal muscle of centrally obese subjects is mediated by alterations in 11βHSD1.

insulin resistance - metabolic syndrome - cortisol - adiponectin

References

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