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Access Type

WSU Access

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

Zhengping Yi

Abstract

Ubiquitin proteasome system is a relatively newly discovered pathway for protein degradation. Many studies have successfully pointed out the critical functions that UPS plays in regulating many physiological processes. On the other hand, recent studies suggested that abnormal UPS activities might be involved in the pathophysiology of several disorders including type 2 diabetes. However, the specific changes in UPS during the development of insulin resistance and consequently T2D are still unclear.

UPS is composed of two major steps, a reversible ubiquitin conjugation to the targeted substrate followed by proteasomal degradation of the ubiquitinated proteins. In this study, we examined the changes in the total ubiquitination as well as the site-specific ubiquitin conjugation under hyperinsulinemic-hyperglycemic conditions in primary skeletal muscle cells derived from lean, healthy people. We observed a significant decrease in the total ubiquitination in case of glucotoxicity, which is a simulation for insulin resistance in cell culture. In addition, we identified 21 ubiquitination sites that showed significant changes upon treatment with different glucose and insulin concentrations. This study provides a list of ubiquitination as a reference for future research in ubiquitination and diabetes in human skeletal muscle cells.

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