Please use this identifier to cite or link to this item:
Title: Glucocorticoid-induced insulin resistance in men is associated with suppressed undercarboxylated osteocalcin.
Austin 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;Levinger, Itamar 
Affiliation: Department of Physiology, University of Sydney, Sydney, NSW, Australia
Mary Mackillop Institute of Health Research, Australian Catholic University, Melbourne, VIC, Australia
Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong, VIC, Australia
Institute of Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia
Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
Monash Centre of Health Research and Implementation (MCHRI), School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
University of Melbourne, Melbourne, VIC, Australia
PathWest QEII Medical Centre, Perth, WA, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
Issue Date: 2019
Date: 2018-08-23
Publication information: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research 2019; 34(1): 49-58
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 post-exercise insulin resistance in part through decreased circulating ucOC and ucOC-mediated skeletal muscle protein signaling. Nine healthy males 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 post-exercise 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 < 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). Glucocorticoids -induced basal and post-exercise 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 Glucocorticoids -induced insulin resistance in human subjects requires further investigation This article is protected by copyright. All rights reserved.
DOI: 10.1002/jbmr.3574
ORCID: 0000-0002-9692-048X
Journal: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
PubMed URL: 30138543
Type: Journal Article
Subjects: Anti-inflammation
Glucocorticoid Metabolism
Glycemic Control
High-intensity Interval Exercise
Insulin Signaling
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Mar 4, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.