کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1929007 | 1536781 | 2012 | 6 صفحه PDF | دانلود رایگان |
The G-protein-coupled receptor kinase 5 (GRK5) is an important member of the threonine/serine kinase family that phosphorylates and regulates the G-protein-coupled receptor (GPCR) signaling pathway. GRK5 is highly expressed in adipose tissue and may act as an adipogenetic factor under high-fat load [1]. Insulin resistance is associated with the pathogenesis of metabolic disorders such as type 2 diabetes and obesity; however, the potential role of GRK5 in insulin resistance is unknown. We characterized the biochemical and molecular alterations related to metabolic complications observed in GRK5−/− mice. These mice, which are partially resistant to obesity induced by a high-fat diet, had impaired glucose tolerance and insulin sensitivity, as well as disruption of AKT signaling transduction compared with their wild-type littermates. Further study showed that the decreased insulin sensitivity was not attributable to alterations in inflammatory status such as the NF-κB signaling pathway or inflammatory gene expression. Instead, hepatic steatosis and changes of mRNA in genes involved in hepatic glucose and lipid homeostasis were found. Overall, our data identified GRK5 as a positive regulator of insulin sensitivity. Our results showed that this protein is a potential therapeutic target in the treatment of insulin resistance and related disorders.
► GRK5 ablation increased insulin resistance.
► GRK5 ablation did not affect inflammatory status of WAT.
► GRK5 ablation lead to hepatic steatosis.
Journal: Biochemical and Biophysical Research Communications - Volume 429, Issues 1–2, 7 December 2012, Pages 99–104