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The Role of the Retinol-Binding Protein Receptor STRA6 in Regulation of Diurnal Insulin Responses

Gliniak, Christy M
http://orcid.org/0000-0003-3806-6112
http://rave.ohiolink.edu/etdc/view?acc_num=case1495817057084695

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Nutrition.
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-erb-alpha. Furthermore, STRA6 is necessary for diurnal rhythmicity of insulin action and JAK/STAT signaling in adipose tissue. These findings establish that holo-RBP and its receptor STRA6 are potent regulators of diurnal insulin responses, and suggest that the holo-RBP/STRA6 signaling axis may represent a novel therapeutic target in type 2 diabetes.
J. Mark Brown (Advisor)
Danny Manor (Committee Chair)
Colleen Croniger (Committee Member)
Roman Kondratov (Committee Member)
Mark Jackson (Committee Member)
133 p.
Nutrition
circadian; insulin; vitamin A; retinol; adipose tissue; janus kinase; STRA6; RBP

Recommended Citations

Citations

  • Gliniak, C. M. (2017). The Role of the Retinol-Binding Protein Receptor STRA6 in Regulation of Diurnal Insulin Responses [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1495817057084695

    APA Style (7th edition)

  • Gliniak, Christy. The Role of the Retinol-Binding Protein Receptor STRA6 in Regulation of Diurnal Insulin Responses. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1495817057084695.

    MLA Style (8th edition)

  • Gliniak, Christy. "The Role of the Retinol-Binding Protein Receptor STRA6 in Regulation of Diurnal Insulin Responses." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1495817057084695

    Chicago Manual of Style (17th edition)

case1495817057084695
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© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.