Homozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Ror alpha (also known as Rora) expression in all tissues, display a lean and dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) alpha action in skeletal muscle was involved in the regulation of glucose metabolism

A Mamontova

AD Baron

AG Smith

AM Jetten

B Friedrich

BA Hamilton

BL Wagner

C Schmitz-Peiffer

C Sztalryd

D An

DA Gold

E Raspe

F Boukhtouche

F Lang

G. E. O. Muscat

GE Muscat

GR Peck

H Cho

H Duez

HS Kang

I Dussault

J Wang

JT Brozinick Jr

LD McBroom

M Bell

M Schwab

M Steinmayr

M. A. Pearen

M. J. Watt

MJ Watt

N Kumar

N Vu-Dac

NE Wolins

OP McGuinness

P Delerive

P Lau

P. Lau

R Bertin

R. L. Fitzsimmons

RS Garofalo

S Andrikopoulos

S Matthaei

S Raichur

U Matysiak-Scholze

English

PubMed

Springer - Publisher Connector

Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle

Lau, P.

Fitzsimmons, R. L.

Pearen, M. A.

Watt, M. J.

Muscat, G. E. O.

University of Queensland eSpace

Crossref

Diabetologia

AIMS/HYPOTHESIS: Homozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Rorα (also known as Rora) expression in all tissues, display a lean and dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) α action in skeletal muscle was involved in the regulation of glucose metabolism. METHODS: We used a three-armed genomic approach, including expression profiling, ingenuity analysis and quantitative PCR validation to identify the signalling pathway(s) in skeletal muscle that are perturbed in sg/sg mice. Moreover, western analysis, functional insulin and glucose tolerance tests, and ex vivo glucose uptake assays were used to phenotypically characterise the impact of aberrant v-AKT murine thymoma viral oncogene homologue (AKT) signalling. RESULTS: Homozygous and heterozygous (sg/sg and sg/+) animals exhibited decreased fasting blood glucose levels, mildly improved glucose tolerance and increased insulin sensitivity. Illumina expression profiling and bioinformatic analysis indicated the involvement of RORα in metabolic disease and phosphatidylinositol 3-kinase-AKT signalling. Quantitative PCR and western analysis validated increased AKT2 (mRNA and protein) and phosphorylation in sg/sg mice in the basal state. This was associated with increased expression of Tbc1d1 and Glut4 (also known as Slc2a4) mRNA and protein. Finally, in agreement with the phenotype, we observed increased (absolute) levels of AKT and phosphorylated AKT (in the basal and insulin stimulated states), and of (ex vivo) glucose uptake in skeletal muscle from sg/sg mice relative to wild-type littermates. CONCLUSIONS/INTERPRETATION: We propose that Rorα plays an important role in regulation of the AKT2 signalling cascade, which controls glucose uptake in skeletal muscle

Lau, P

Fitzsimmons, RL

Pearen, MA

Watt, MJ

Muscat, GEO

University of Melbourne Institutional Repository

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http://minerva-access.unimelb.edu.au/bitstream/11343/270341/1/PMC3071927.pdf

Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle

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Springer - Publisher Connector

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University of Melbourne Institutional Repository