Date of Award

1-1-2011

Document Type

Campus Access Thesis

Department

Exercise Science

First Advisor

James Carson

Abstract

The formation of 2-(succinyl)cysteine (2SC), through a process called succination, takes place in obese and diabetic conditions when a cell is in a state of nutrient excess. This stable, post-translational modification is formed through irreversible reactions between fumarate and cysteine residues on proteins. Although 2SC is found in normal tissues, increased nutrients cause a back up of the electron transport chain (ETC) and a buildup of Krebs cycle intermediates, including fumarate. Previously, we have seen increased succination in adipose tissue of the db/db type 2 diabetic mouse model. Consequently, this study focuses on the distribution of 2SC within various organs, skeletal muscles, and adipose tissues of the db/db mouse. In addition, another type 2 diabetic model, the ob/ob mouse, as well as a diet induced obese (DIO) model were examined to determine if differences in succination could be detected. Previous research also shows evidence of increased succination in the streptozotocin-induced (STZ) diabetic mouse. In this study, epididymal adipocytes were extracted from both STZ and Akita type 1 models, and analyzed for succinated protein. We found that protein succination only increased in adipose tissue of the type 2 models as well as the DIO models. No changes in succination were detected in type 1 animals. In addition, brown and white adipose tissues from hibernating, 13-lined ground squirrels were tested to determine if obesity in the absence of hyperglycemia affected succination of protein. Results showed that succination did not vary in neither brown nor white adipose tissue, independent of if the animals were hibernating, recovering, or arousing from torpor. These results indicate that both hyperglycemia and insulin resistance are necessary for succination of protein. As such, we propose that succination could be used as a biomarker for mitochondrial stress in type 2 diabetes and pre-diabetes.

Rights

© 2011, Sonia Thomas

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