Glucocorticoid-induced insulin resistance in men is associated with suppressed undercarboxylated osteocalcin
Journal article
Parker, Lewan, Lin, Xuzhu, Garnham, Andrew, McConell, Glenn, Stepto, Nigel K., Hare, David L., Byrnes, Elizabeth, Ebeling, Peter R., Seeman, Ego, Brennan-Speranza, Tara C. and Levinger, Itamar. (2019). Glucocorticoid-induced insulin resistance in men is associated with suppressed undercarboxylated osteocalcin. Journal of Bone and Mineral Research. 34(1), pp. 49-58. https://doi.org/10.1002/jbmr.3574
Authors | Parker, Lewan, Lin, Xuzhu, Garnham, Andrew, McConell, Glenn, Stepto, Nigel K., Hare, David L., Byrnes, Elizabeth, Ebeling, Peter R., Seeman, Ego, Brennan-Speranza, Tara C. and Levinger, Itamar |
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Abstract | In mice, glucocorticoid‐induced insulin resistance occurs largely through impaired osteoblast function and decreased circulating undercarboxylated osteocalcin (ucOC). Whether these mechanisms contribute to glucocorticoid‐induced insulin resistance in humans has yet to be established. In addition, the effects of glucocorticoids on the exercise‐induced increase in circulating ucOC and insulin sensitivity are also unknown. We hypothesized that acute glucocorticoid treatment would lead to basal and postexercise insulin resistance in part through decreased circulating ucOC and ucOC‐mediated skeletal muscle protein signaling. Nine healthy men completed two separate cycling sessions 12 hours after ingesting either glucocorticoid (20 mg prednisolone) or placebo (20 mg Avicel). The homeostatic model assessment was used to assess basal insulin sensitivity and a 2‐hour euglycemic–hyperinsulinemic clamp was commenced 3 hours after exercise to assess postexercise insulin sensitivity. Serum ucOC and skeletal muscle protein signaling were measured. Single‐dose glucocorticoid ingestion increased fasting glucose (27%, p < 0.01) and insulin (83%, p < 0.01), and decreased basal insulin sensitivity (−47%, p < 0.01). Glucocorticoids reduced insulin sensitivity after cycling exercise (−34%, p < 0.01), reduced muscle GPRC6A protein content (16%, p < 0.05), and attenuated protein phosphorylation of mTORSer2481, AktSer374, and AS160Thr642 (59%, 61%, and 50%, respectively; all p s < 0.05). Serum ucOC decreased (−24%, p < 0.01) which correlated with lower basal insulin sensitivity (r = 0.54, p = 0.02), lower insulin sensitivity after exercise (r = 0.72, p < 0.05), and attenuated muscle protein signaling (r = 0.48–0.71, p < 0.05). Glucocorticoid‐induced basal and postexercise insulin resistance in humans is associated with the suppression of circulating ucOC and ucOC‐linked protein signaling in skeletal muscle. Whether ucOC treatment can offset glucocorticoid‐induced insulin resistance in human subjects requires further investigation. © 2018 American Society for Bone and Mineral Research. |
Keywords | glucocorticoid metabolism; anti-inflammation; glycemic control; high-intensity interval exercise; insulin signaling |
Year | 2019 |
Journal | Journal of Bone and Mineral Research |
Journal citation | 34 (1), pp. 49-58 |
Publisher | John Wiley & Sons |
ISSN | 0884-0431 |
Digital Object Identifier (DOI) | https://doi.org/10.1002/jbmr.3574 |
Scopus EID | 2-s2.0-85053517542 |
Open access | Published as green open access |
Page range | 49-58 |
Funder | Victoria University |
National Heart Foundation of Australia | |
Deakin University | |
Collaborative Research Networks (CRN), Australian Government | |
Research Group | Mary MacKillop Institute for Health Research |
Author's accepted manuscript | License All rights reserved File Access Level Open |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 17 Sep 2018 |
Publication process dates | |
Accepted | 08 Aug 2018 |
Grant ID | 100040 |
https://acuresearchbank.acu.edu.au/item/87y61/glucocorticoid-induced-insulin-resistance-in-men-is-associated-with-suppressed-undercarboxylated-osteocalcin
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File access level: Open |
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