title: GRK5 ablation contributes to insulin resistance.
abstract: 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.
authors.affiliation: The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Minjie
authors.initials: M
authors.lastname: Shen
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D007328:Insulin; D054774:G-Protein-Coupled Receptor Kinase 5; C517895:Grk5 protein, mouse; D005947:Glucose