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Uncarboxylated osteocalcin enhances glucose uptake ex vivo in insulin-stimulated mouse oxidative but not glycolytic muscle

journal contribution
posted on 2018-08-01, 00:00 authored by Xuzhu Lin, Lewan ParkerLewan Parker, Emma Mclennan, Xinmei Zhang, Alan Hayes, Glenn McConell, Tara C Brennan-Speranza, Itamar Levinger
Uncarboxylated osteocalcin (ucOC) stimulates muscle glucose uptake in mice EDL and soleus muscles. However, whether ucOC also exerts a similar effect in insulin-stimulated muscles in a muscle type-specific manner is currently unclear. We aimed to test the hypothesis that, with insulin stimulation, ucOC per se has a greater effect on oxidative muscle compared with glycolytic muscle, and to explore the underlying mechanisms. Mouse (C57BL6, male 9-12 weeks) extensor digitorum longus (EDL) and soleus muscles were isolated and longitudinally split into halves. Muscle samples were treated with varying doses of recombinant ucOC (0, 0.3, 1, 3, 30 ng/ml), followed by insulin addition. Muscle glucose uptake, protein phosphorylation and total expression of protein kinase B (Akt), Akt substrate of 160 kDa (AS160), extracellular signal-regulated kinase isoform 2 (ERK2), and adenosine monophosphate-activated protein kinase subunit α (AMPKα) were assessed. ucOC treatment at 30 ng/ml enhanced muscle glucose uptake in insulin-stimulated soleus, a mainly oxidative muscle (17.5%, p < 0.05), but not in EDL-a mostly glycolytic muscle. In insulin-stimulated soleus only, ucOC treatment (3 and 30 ng/ml) increased phosphorylation of AS160 and ERK2, but not Akt or AMPKα. The ucOC-induced increase in ERK2 phosphorylation in soleus was not associated with the increase in glucose uptake or AS160 phosphorylation. ucOC enhances glucose uptake and AS160 phosphorylation in insulin-stimulated oxidative but not glycolytic muscle, via upstream mechanisms which appear to be independent of ERK or AMPK.

History

Journal

Calcified tissue international

Volume

103

Pagination

198-205

Location

New York, N.Y.

ISSN

0171-967X

eISSN

1432-0827

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, Springer Science+Business Media, LLC, part of Springer Nature

Issue

2

Publisher

Springer