Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ß-cells.
Diabetes
; 59(11): 2854-61, 2010 Nov.
Article
en En
| MEDLINE
| ID: mdl-20798333
OBJECTIVE: Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic ß-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion. RESEARCH DESIGN AND METHODS: To elucidate the function of RXRs in pancreatic ß-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRß was inducibly expressed in pancreatic ß-cells using the Tet-On system. We also established a pancreatic ß-cell line from an insulinoma caused by the ß-cell-specific expression of simian virus 40 T antigen in the above transgenic mouse. RESULTS: In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic ß-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of ß-cells. CONCLUSIONS: These results suggest that endogenous RXR negatively regulates the glucose-stimulated insulin secretion. Given these findings, we propose that the modulation of endogenous RXR in ß-cells may be a new therapeutic approach for improving impaired insulin secretion in type 2 diabetes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores X Retinoide
/
Células Secretoras de Insulina
/
Glucosa
/
Insulina
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Diabetes
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos