Dataset Information

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.

ABSTRACT: Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160?kDa (AS160) signaling cascade. Extensor digitorum longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had no significant effect on the phosphorylation of AMPK? (Thr172). The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

SUBMITTER: Lin X

PROVIDER: S-EPMC5698688 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.

Lin Xuzhu X Parker Lewan L Mclennan Emma E Zhang Xinmei X Hayes Alan A McConell Glenn G Brennan-Speranza Tara C TC Levinger Itamar I

Frontiers in endocrinology 20171122

Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic ...[more]

PMID: 29204135

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Project description:gene expression profile in diaphragm (DIA), extensor digitorum longus (EDL) and extraocular (EOM) muscles of rats with actively induced experimentally acquired MG (EAMG) using Affymetrix rat RAE230 gene chip. Experiment Overall Design: Total RNA was obtained with TRIzol (Invitrogen Carlsbad, CA) following the manufacturers recommended protocol. Tissues from 3 animals were combined into each RNA sample to decrease inter-subject variability. RNA pellets were cleaned by RNasey kits and resuspended at 1 Î¼g RNA/Î¼l DEPC-treated water and 5 ug was used in a reverse transcription reaction (SuperScript II; Life Technologies, Rockville, MD) to generate first strand cDNA. Double strand cDNA was synthesized and used in an in vitro transcription (IVT) reaction to generate biotinylated cRNA. Fragmented cRNA (15 ug) was used in a 300 ul hybridization cocktail containing herring sperm DNA and BSA as carrier molecules, spiked IVT controls, and buffering agents. A 200 ul aliquot of this cocktail was used for hybridization to Affymetrix rat REA230 (Santa Clara, CA) microarrays for 16 hrs at 45o C. The manufacturerâs standard post-hybridization wash, double-stain, and scanning protocols used an Affymetrix GeneChip Fluidics Station 400 and a Hewlett Packard Gene Array scanner. Experiment Overall Design: Microarray data analysis Experiment Overall Design: Raw data from microarray scans were analyzed with Affymetrix GCOS 2.0. GCOS evaluates sets of perfect match (PM) and mismatch (MM) probe sequences to obtain both hybridization signal values and present/absent calls for each transcript. Microarrays were scaled to the same target intensity and pairwise comparisons were made between experimental and control samples. Comparisons the one-sided Wilcoxonâs signed rank test to estimate âincrease/no change/ decreaseâ difference calls for each pair-wise comparison. Transcripts defined as differentially regulated met the criteria of: (a) consistent increase/decrease call across 7 out of 9 replicate comparisons, based upon Wilcoxonâs signed rank test (algorithm assesses probe pair saturation, calculates a p value and determines increase, decrease, or no change calls) and (b) the average fold difference â¥ 2.0. Data were visualized as a hierarchical dendrogram generayed on computer (Genespring software,ver 7.2; Silicon Genetics, Redwood city, CA). Annotation was done according to Affymetrix NetAffyx Gene Ontology database.

Dataset Information

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.

Publications

Recombinant Uncarboxylated Osteocalcin <i>Per Se</i> Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.

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