Uncarboxylated Osteocalcin Enhances Glucose Uptake Ex Vivo in Insulin-Stimulated Mouse Oxidative But Not Glycolytic Muscle

Lin, X, Parker, L, Mclennan, E, Zhang, X, Hayes, A, McConell, G, Brennan-Speranza, T and Levinger, I 2018, 'Uncarboxylated Osteocalcin Enhances Glucose Uptake Ex Vivo in Insulin-Stimulated Mouse Oxidative But Not Glycolytic Muscle', Calcified Tissue International, vol. 103, no. 2, pp. 198-205.


Document type: Journal Article
Collection: Journal Articles

Title Uncarboxylated Osteocalcin Enhances Glucose Uptake Ex Vivo in Insulin-Stimulated Mouse Oxidative But Not Glycolytic Muscle
Author(s) Lin, X
Parker, L
Mclennan, E
Zhang, X
Hayes, A
McConell, G
Brennan-Speranza, T
Levinger, I
Year 2018
Journal name Calcified Tissue International
Volume number 103
Issue number 2
Start page 198
End page 205
Total pages 8
Publisher Springer New York LLC
Abstract 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 alpha (AMPK alpha) 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 AMPK alpha. 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.
Subject Cell Metabolism
Keyword(s) AS160
ERK
Glucose uptake
Insulin stimulation
Skeletal muscle type
Uncarboxylated osteocalcin
DOI - identifier 10.1007/s00223-018-0400-x
Copyright notice © Springer Science+Business Media, LLC, part of Springer Nature 2018
ISSN 0171-967X
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