The Role of the Retinol-Binding Protein Receptor STRA6 in Regulation of Diurnal Insulin Responses
Year: 2017
Type: article
Abstract: It has long been appreciated that insulin action is closely tied to circadian rhythms.However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood.Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes.RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body.The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells.Coupled to retinol transport, holo-RBP can activate STRA6-driven janus kinase (JAK) signaling and downstream induction of signal transducer and activator of transcription (STAT) target genes.STRA6 signaling in white adipose tissue has been shown to inhibit insulin receptor responses.Here we examined diurnal rhythmicity of the RBP4-STRA6 signaling axis, and investigated whether STRA6 is necessary for diurnal variations in insulin sensitivity.We show that adipose tissue STRA6 undergoes circadian patterning driven in part by the nuclear transcription factor Rev-erbα.Furthermore, STRA6 is necessary for diurnal rhythmicity of insulin action and JAK/STAT signaling in adipose tissue.These findings establish that
Author: Christy M. Gliniak
Institution: Case Western Reserve University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2807664449