PMID- 30908701
OWN - NLM
STAT- MEDLINE
DCOM- 20200813
LR  - 20200813
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 34
IP  - 8
DP  - 2019 Aug
TI  - Undercarboxylated Osteocalcin Improves Insulin-Stimulated Glucose Uptake in 
      Muscles of Corticosterone-Treated Mice.
PG  - 1517-1530
LID - 10.1002/jbmr.3731 [doi]
AB  - Short-term administration of glucocorticoids (GCs) impairs muscle insulin 
      sensitivity at least in part via the reduction of undercarboxylated osteocalcin 
      (ucOC). However, whether ucOC treatment reverses the GC-induced muscle insulin 
      resistance remains unclear. To test the hypothesis that ucOC directly ameliorates 
      impaired insulin-stimulated glucose uptake (ISGU) induced by short-term GC 
      administration in mice muscle and to identify the molecular mechanisms, mice were 
      implanted with placebo or corticosterone (CS) slow-release pellets. Two days 
      post-surgery, insulin-tolerance tests (ITTs) were performed. On day 3, serum was 
      collected and extensor digitorum longus (EDL) and soleus muscles were isolated 
      and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 microU/mL), or both. 
      Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins 
      were assessed. CS administration reduced both serum osteocalcin and ucOC levels, 
      whole-body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment 
      restored ISGU in CS-affected muscle, without increasing non-insulin-stimulated 
      glucose uptake. In CS-affected EDL muscle, ucOC enhanced insulin action on 
      phosphorylated (p-)protein kinase B (Akt)(Ser473) and the p-extracellular 
      signal-regulated kinase isoform 2 (ERK2)(Thr202/Tyr204) /total (t)ERK2 ratio, 
      which correlated with ISGU. In CS-affected soleus muscle, ucOC enhanced insulin 
      action on p-mammalian target of rapamycin (mTOR)(Ser2481) , the p-mTOR(Ser2481) 
      /tmTOR ratio, p-Akt substrate of 160kD (AS160)(Thr642) , and p-protein kinase C 
      (PKC) (pan)(Thr410) , which correlated with ISGU. Furthermore, p-PKC 
      (pan)(Thr410) correlated with p-Akt(Ser473) and p-AS160(Thr642) . ucOC exerts 
      direct insulin-sensitizing effects on CS-affected mouse muscle, likely through an 
      enhancement in activity of key proteins involved in both insulin and ucOC 
      signaling pathways. Furthermore, these effects are muscle type-dependent. (c) 2019 
      American Society for Bone and Mineral Research.
CI  - (c) 2019 American Society for Bone and Mineral Research.
FAU - Lin, Xuzhu
AU  - Lin X
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
FAU - Parker, Lewan
AU  - Parker L
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
AD  - Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong, 
      VIC, Australia.
FAU - McLennan, Emma
AU  - McLennan E
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
FAU - Hayes, Alan
AU  - Hayes A
AUID- ORCID: 0000-0003-1398-3694
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
AD  - College of Health and Biomedicine, Victoria University, Melbourne, VIC, 
      Australia.
AD  - Department of Medicine-Western Health, Australian Institute for Musculoskeletal 
      Science (AIMSS), Melbourne Medical School, The University of Melbourne, 
      Melbourne, VIC, Australia.
FAU - McConell, Glenn
AU  - McConell G
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
FAU - Brennan-Speranza, Tara C
AU  - Brennan-Speranza TC
AD  - Department of Physiology and Bosch Institute for Medical Research, University of 
      Sydney, Australia.
FAU - Levinger, Itamar
AU  - Levinger I
AUID- ORCID: 0000-0001-9194-2033
AD  - Institute of Health and Sport (IHES), Victoria University, Melbourne, Australia.
AD  - Department of Medicine-Western Health, Australian Institute for Musculoskeletal 
      Science (AIMSS), Melbourne Medical School, The University of Melbourne, 
      Melbourne, VIC, Australia.
LA  - eng
GR  - 100040/Australian Heart Fundation/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190612
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Insulin)
RN  - 104982-03-8 (Osteocalcin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adrenal Cortex Hormones/*pharmacology
MH  - Animals
MH  - Delayed-Action Preparations/pharmacology
MH  - Glucose/*metabolism
MH  - Insulin/*pharmacology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mice
MH  - Muscle, Skeletal/*metabolism
MH  - Osteocalcin/*metabolism
OTO - NOTNLM
OT  - GLUCOCORTICOID
OT  - INSULIN SENSITIVITY
OT  - INSULIN SIGNALING PATHWAY
OT  - SKELETAL MUSCLE
OT  - UCOC SIGNALING PATHWAY
OT  - UNDERCARBOXYLATED OSTEOCALCIN
EDAT- 2019/03/26 06:00
MHDA- 2020/08/14 06:00
CRDT- 2019/03/26 06:00
PHST- 2018/12/07 00:00 [received]
PHST- 2019/03/18 00:00 [revised]
PHST- 2019/03/20 00:00 [accepted]
PHST- 2019/03/26 06:00 [pubmed]
PHST- 2020/08/14 06:00 [medline]
PHST- 2019/03/26 06:00 [entrez]
AID - 10.1002/jbmr.3731 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2019 Aug;34(8):1517-1530. doi: 10.1002/jbmr.3731. Epub 2019 Jun 
      12.