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RNASE L MEDIATES GLUCOSE HOMEOSTASIS THROUGH REGULATING THE INSULIN SIGNALING PATHWAY

Liu, Danting
http://rave.ohiolink.edu/etdc/view?acc_num=csu1544627440336052

Abstract Details

2018, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Diabetes is characterized by hyperglycemia mainly due to defect in insulin secretion and/or action. Regulation of glucose transport and use by insulin is central to the maintenance of whole-body glucose homeostasis. One of the potential mechanisms associated with insulin sensitivity is the activation of insulin receptor (IR) and subsequently transduces the signal through phosphorylation of insulin receptor substrate (IRS) and activation of the PI-3K/Akt pathway. In contrast, activation of the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K) suppresses the signal cascade. RNase L, an interferon (IFN)-inducible enzyme, plays an important role in IFN functions against viral infection and cell proliferation. However, a direct link between RNase L and insulin sensitivity has yet to be clearly established. RNase L+/+ and -/- mouse embryonic fibroblasts (MEFs) and hepatocytes were used to investigate the role of RNase L in insulin signaling and sensitivity. Cells were treated with insulin at various time points and different concentrations. Activation of the insulin signaling pathway was determined by immunoblot analyses for the protein level and phosphorylation status of these components such as IR/p-IR, IRS1/p-IRS1 and AKT/p-AKT in the presence or absence of a chemical inhibitor. Interestingly, we found that RNase L might mediate insulin signaling and glucose homeostasis through impacting insulin receptor (IR) which is a trans-membrane receptor activated by insulin. The phosphorylation status of IR was significantly reduced in the cell deficient RNase L. As a result, activation of downstream components in the insulin signaling pathway and the PI3K/AKT pathway was significantly inhibited in RNase L-/- cells. Further investigation of the molecular mechanism underlying the role of RNase L in mediating the activation of IR revealed that RNase L might regulate cleaving the precursor of IR and activating IRS-1 via the ubiquitin/ proteasome system. Our results obtained from this study provide a better understanding of RNase L functions and open a new horizon for its role in the metabolic system besides in the defense of viral infection.
Aimin Zhou (Committee Chair)
Michael Kalafatis (Committee Member)
Bin Su (Committee Member)
Xue-Long Sun (Committee Member)
Nolan Holland (Committee Member)
126 p.
Biochemistry; Molecular Biology
RNASE L; Insulin Resistance; Insulin Receptor;

Recommended Citations

Citations

  • Liu, D. (2018). RNASE L MEDIATES GLUCOSE HOMEOSTASIS THROUGH REGULATING THE INSULIN SIGNALING PATHWAY [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1544627440336052

    APA Style (7th edition)

  • Liu, Danting. RNASE L MEDIATES GLUCOSE HOMEOSTASIS THROUGH REGULATING THE INSULIN SIGNALING PATHWAY. 2018. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1544627440336052.

    MLA Style (8th edition)

  • Liu, Danting. "RNASE L MEDIATES GLUCOSE HOMEOSTASIS THROUGH REGULATING THE INSULIN SIGNALING PATHWAY." Doctoral dissertation, Cleveland State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=csu1544627440336052

    Chicago Manual of Style (17th edition)

csu1544627440336052
192
© 2018, some rights reserved.Creative Commons License RNASE L MEDIATES GLUCOSE HOMEOSTASIS THROUGH REGULATING THE INSULIN SIGNALING PATHWAY by Danting Liu is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Cleveland State University and OhioLINK.