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

Autor:	Lin, Xuzhu, Parker, Lewan, Mclennan, Emma, Zhang, Xinmei, Hayes, Alan, McConell, Glenn, Brennan-Speranza, Tara C., Levinger, Itamar
Předmět:	OSTEOCALCIN PHYSIOLOGICAL effects of glucose OXIDATIVE stress MUSCLE physiology PHYSIOLOGICAL effects of insulin LABORATORY mice OXYGEN metabolism ANIMAL experimentation BIOLOGICAL transport CELLULAR signal transduction COMPARATIVE studies DEOXY sugars GLUCOSE GLYCOLYSIS HYPOGLYCEMIC agents INSULIN RESEARCH methodology MEDICAL cooperation MICE PHOSPHORYLATION RESEARCH TRANSFERASES EVALUATION research SKELETAL muscle PHARMACODYNAMICS
Zdroj:	Calcified Tissue International; Aug2018, Vol. 103 Issue 2, p198-205, 8p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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