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Randomized study data advance understanding of glucocorticoids
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Glucocorticoids act differently on muscle and adipose tissue, increasing insulin sensitivity in subcutaneous adipose tissue but inducing resistance in skeletal muscle, according to data from a double blind, randomized, placebo-controlled, crossover study presented at the Society for Endocrinology BES 2012 meeting.
The different actions of steroids present possible avenues of research to develop anti-inflammatory therapies that do not cause weight gain typically associated with the use of steroids, according to Jeremy Tomlinson, MRCP, PhD, researcher and medical research council senior clinical fellow and consultant endocrinologist in the Centre for Endocrinology, Diabetes and Metabolism at the School of Clinical and Experimental Medicine, University of Birmingham, United Kingdom.
“In fat tissue, hydrocortisone worked with insulin to enhance its action, its suppression of the breakdown of fat,” Tomlinson told Endocrine Today, noting that he and colleagues have previously demonstrated that glucocorticoids had a dissimilar effect on muscle tissue and adipose tissue in vitro. “We wanted to test this in a clinical study.”
Fifteen volunteers with a mean age of 33 years and a mean BMI of 26.6 underwent random assignment, receiving an initial injection of either hydrocortisone (0.2 mg/kg/hour) or saline overnight. Serving as their own controls, they later received an infusion of the reverse therapy.
They performed adipose tissue microdialysis to determine insulin-stimulated pyruvate generation and insulin-mediated suppression of glycerol release.
In adipose tissue, in the fasting state, pyruvate release was similar between steroids and saline. Insulin-stimulated pyruvate release (99 ± 13 mcmol/L/hour vs. 136 ± 20 mcmol/L/hour; P<.05) was significantly enhanced after overnight steroid infusion consistent with insulin sensitization (36 ± 14 mcmol/L/hour vs. 186 ± 29 mcmol/L/hour; P<.001). Steroid infusion elevated adipose tissue lipolysis (235 ± 47 mcmol/L/hour vs. 365 ± 53 mcmol/L/hour; P=.05), which was suppressed by insulin. This was significantly enhanced, however, after overnight steroid infusion (114 ± 25 mcmol/L/hour vs. 196 ± 39 mcmol/L/hour; P=.05).
“It is not the case that glucocorticoids do the same thing in all tissues,” Tomlinson said.
Stephen Atkin, MD, PhD, FRCP, head of academic endocrinology, diabetes and metabolism at Hull York Medical School, Hull, United Kingdom, said the different influence of steroids presents a possible direction for the development of new molecules, and it would be interesting to observe whether a similar differential effect occurs with visceral fat, which is regarded as a major determinant of cardiovascular risk.
“They have shown that there is a different effect of the glucocorticoids, depending on the tissue they are acting upon,” Atkin told Endocrine Today. “This is what happens in subcutaneous fat. We don’t know if visceral fat would respond in the same way.” – by Louise Gagnon
Disclosure: Drs. Tomlinson and Atkin report no relevant financial disclosures.
For more information:
- Hazlehurst J. Abstract #OC4.7. Presented at: the Society for Endocrinology BES meeting; March 19-22, 2012; Harrogate, United Kingdom.