Your browser doesn't support javascript.
loading
FMK, an Inhibitor of p90RSK, Inhibits High Glucose-Induced TXNIP Expression via Regulation of ChREBP in Pancreatic ß Cells.
Han, Jung-Hwa; Kim, Suji; Kim, Sujin; Lee, Heejung; Park, So-Young; Woo, Chang-Hoon.
Afiliación
  • Han JH; Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
  • Kim S; Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
  • Kim S; Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
  • Lee H; Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
  • Park SY; Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
  • Woo CH; Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Daegu 42415, Korea.
Int J Mol Sci ; 20(18)2019 Sep 09.
Article en En | MEDLINE | ID: mdl-31505737
Hyperglycemia is the major characteristic of diabetes mellitus, and a chronically high glucose (HG) level causes ß-cell glucolipotoxicity, which is characterized by lipid accumulation, impaired ß-cell function, and apoptosis. TXNIP (Thioredoxin-interacting protein) is a key mediator of diabetic ß-cell apoptosis and dysfunction in diabetes, and thus, its regulation represents a therapeutic target. Recent studies have reported that p90RSK is implicated in the pathogenesis of diabetic cardiomyopathy and nephropathy. In this study, we used FMK (a p90RSK inhibitor) to determine whether inhibition of p90RSK protects ß-cells from chronic HG-induced TXNIP expression and to investigate the molecular mechanisms underlying the effect of FMK on its expression. In INS-1 pancreatic ß-cells, HG-induced ß-cell dysfunction, apoptosis, and ROS generation were significantly diminished by FMK. In contrast BI-D1870 (another p90RSK inhibitor) did not attenuate HG-induced TXNIP promoter activity or TXNIP expression. In addition, HG-induced nuclear translocation of ChREBP and its transcriptional target molecules were found to be regulated by FMK. These results demonstrate that HG-induced pancreatic ß-cell dysfunction resulting in HG conditions is associated with TXNIP expression, and that FMK is responsible for HG-stimulated TXNIP gene expression by inactivating the regulation of ChREBP in pancreatic ß-cells. Taken together, these findings suggest FMK may protect against HG-induced ß-cell dysfunction and TXNIP expression by ChREBP regulation in pancreatic ß-cells, and that FMK is a potential therapeutic reagent for the drug development of diabetes and its complications.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Proteínas de Ciclo Celular / Proteínas Quinasas S6 Ribosómicas 90-kDa / Inhibidores de Proteínas Quinasas / Células Secretoras de Insulina / Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Glucosa Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2019 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Proteínas de Ciclo Celular / Proteínas Quinasas S6 Ribosómicas 90-kDa / Inhibidores de Proteínas Quinasas / Células Secretoras de Insulina / Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Glucosa Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2019 Tipo del documento: Article Pais de publicación: Suiza