Health, Exercise, and Sports Sciences ETDs

Publication Date

Spring 5-12-2018

Abstract

Objectives: Recently, a malfunction of the autophagic pathway has been implicated with impaired glucose metabolism and progression from prediabetes to type 2 diabetes. Further, an interconnection has been suggested between the autophagy and heat shock protein (HSP) systems. The aims of the present study were to investigate the effects of exercise and rapamycin treatment (RAPA) on the autophagic process and HSP in peripheral blood mononuclear cells (PBMCs) from prediabetics compared to controls. Methods: Two groups matched for age and sex served as subjects and consisted of six prediabetic (42.4±11.7) and six controls (44.4±11.9). Subjects exercised at 50% of VO2max for 60 min with 5 min of rest dispersed every 20 min. PBMCs were isolated pre-exercise, immediately post-exercise, and 4hr after exercise recovery. Additional PBMCs were either exposed to bafilomycin (BAF), rapamycin with bafilomycin (RAPA), or no treatment (NT) with vehicle (dimethylsulfoxide). Proteins and mRNA were analyzed via western blot and quantitative real-time polymerase chain reaction. Results: Exercise increased autophagy immediately post-exercise and recovered 4hr after exercise in control subjects but not in prediabetics. Prediabetic and control subjects both increased autophagy following RAPA treatment; however, a significantly impaired response was observed in prediabetics when compared to controls. No significant differences in HSP72 response was observed. Conclusions: Our results indicate an impairment in autophagic flux but not HSP in PBMCs from prediabetics when compared to controls in response to both exercise and RAPA treatment. Future methods of autophagic upregulation should be investigated to spare malfunctions in autophagy in prediabetics.

Keywords

Autophagy, HSP, Exercise, Rapamycin, PBMC, Prediabetes

Document Type

Dissertation

Language

English

Degree Name

Physical Education, Sports and Exercise Science

Level of Degree

Doctoral

Department Name

Health, Exercise, and Sports Sciences

First Committee Member (Chair)

Christine Mermier

Second Committee Member

Len Kravitz

Third Committee Member

Karol Dokladny

Fourth Committee Member

Fabiano Amorim

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