Effects of Rexinoids on Glucose Transport and Insulin-mediated Signaling in Skeletal Muscles of Diabetic (db/db) Mice

Shen, Qi; Cline, Gary W.; Shulman, Gerald I.; Leibowitz, Mark D.; Davies, Peter J.

doi:10.1074/jbc.m311729200

Cited by 51 publications

(49 citation statements)

References 50 publications

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“…21 Recent studies from some of our laboratories demonstrated that skeletal muscle was a major target of rexinoid action, where it sensitized insulindependent glucose disposal in diabetic skeletal muscle. 32,33 The underlying mechanism of the muscle insulin sensitization involves post-translational activation of several components of insulin signaling involved in glucose uptake. 33 Such amelioration of insulin signaling is afforded via the coordinated regulation of gene expression by rexinoids in skeletal muscles.…”

Section: Rxrs In Skeletal Musclementioning

confidence: 99%

“…32,33 The underlying mechanism of the muscle insulin sensitization involves post-translational activation of several components of insulin signaling involved in glucose uptake. 33 Such amelioration of insulin signaling is afforded via the coordinated regulation of gene expression by rexinoids in skeletal muscles. In a microarray analysis of gene expression in cultured C2C12 myotubules, a synthetic rexinoid, LG100268, most prominently regulated sets of genes involved in fatty acid and cholesterol metabolism, apoptosis and cell cycle regulation, mitochondrial energy metabolism and genes in muscle structure and contractility (Narkar et al, unpublished observation).…”

Section: Rxrs In Skeletal Musclementioning

confidence: 99%

“…21,30,31 However, later a clear difference could be detected in the tissue-specific gene expression patterns induced by the two drugs when compared. 32,33 Studies on RXR homodimers and observations in RXR agonist-treated animals revealed that RXR-specific signaling might exist and may serve as target for new therapeutic approaches. It would be critical to understand how the potentially pleiotropic rexinoids work and if there are processes regulated only by RXR, and to understand the therapeutic potential of this class of drugs.…”

Section: Introductionmentioning

confidence: 99%

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Retinoid X receptors: X-ploring their (patho)physiological functions

Szántó

Narkar²,

Shen³

et al. 2004

Cell Death Differ

256

242

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Retinoid X receptor (RXR) belongs to a family of ligandactivated transcription factors that regulate many aspects of metazoan life. A class of nuclear receptors requires RXR as heterodimerization partner for their function. This places RXR in the crossroad of multiple distinct biological pathways. This and the fact that the debate on the endogenous ligand requirement for RXR is not yet settled make RXR still an enigmatic transcription factor. Here, we review some of the biology of RXR. We place RXR into the evolution of nuclear receptors, review structural details and ligands of the receptor. Then processes regulated by RXR are discussed focusing on the developmental roles deduced from studies on knockout animals and metabolic roles in diseases such as diabetes and atherosclerosis deduced from pharmacological studies. Finally, aspects of RXR's involvement in myeloid differentiation and apoptosis are summarized along with issues on RXR's suitability as a therapeutic target.

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Section: Rxrs In Skeletal Musclementioning

confidence: 99%

Section: Rxrs In Skeletal Musclementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retinoid X receptors: X-ploring their (patho)physiological functions

Szántó

Narkar²,

Shen³

et al. 2004

Cell Death Differ

256

242

View full text Add to dashboard Cite

show abstract

“…Por otra parte, algunos estudios demuestran que el bexaroteno, a través de su acción sobre receptores PPAR del tejido graso, mejora la sensibilidad a la insulina y puede llegar en sujetos diabéticos a disminuir sus necesidades de insulina exógena (12). Incluso, algunos autores han propuesto, que podrían emplearse estos fármacos en el tratamiento de la diabetes mellitus tipo 2 (7).…”

Section: Tabla IIunclassified

Tratamiento del linfoma cutáneo de células T con ligandos selectivos del receptor retinoide X: alteraciones endocrinológicas y metabólicas

Pérez

López

Nevado

et al. 2007

An. Med. Interna (Madrid)

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Avilés Pérez MD, Luna López V, Rodríguez Nevado I, de Argila Fernández-Durán D, Díaz Pérez de Madrid J. Tratamiento del linfoma cutá-neo de células T con ligandos selectivos del receptor retinoide X: alteraciones endocrinológicas y metabólicas. An Med Interna (Madrid) 2007; 24: 595-598. RESUMENLos ligandos selectivos del receptor retinoide X se utilizan actualmente en el tratamiento de estadios avanzados del linfoma cutáneo de células T resistentes a otros tratamientos sistémicos, siendo el bexaroteno el primer fármaco de este grupo aprobado en Europa. Se han descrito numerosos efectos adversos asociados a su utilización, entre los que destacan las alteraciones endocrino-metabólicas. Presentamos a 2 pacientes con linfoma cutáneo de células T, tratados con bexaroteno, que desarrollaron hipotiroidismo central y dislipemia de forma precoz tras su inicio. Se describen también la respuesta de estas alteraciones al tratamiento y su remisión completa tras suspender el bexaroteno.PALABRAS CLAVE: Linfoma cutáneo de células B. Ligando selectivo del receptor retinoide X. Bexaroteno. Hipotiroidismo central. ABSTRACTThe

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“…Por lo tanto, la utilización de estos fármacos en humanos podría tener un efecto favorable tanto en el manejo de las dislipidemias como en la prevención y el tratamiento de la ateroesclerosis. Además, la activación farmacológica de RXR mejora significativamente el control glicémico en animales diabéticos 57 .…”

Section: A R T í C U L Ounclassified