Effect of Acute Aerobic Exercise and Rapamycin Treatment on Autophagy in Peripheral Blood Mononuclear Cells of Adults With Prediabetes

Objectives: Recently, a malfunction of the autophagic pathway has been implicated with impaired glucose metabolism and progression from prediabetes to type 2 diabetes. The aims of this study were to investigate the effect of exercise and rapamycin (RAPA) treatment on the autophagic process in peripheral blood mononuclear cells (PBMCs) from people with prediabetes compared with control subjects. Methods: Two groups matched for age and sex served as participants and included 6 participants with prediabetes (42.4+11.7 years) and 6 control subjects (44.4+11.9 years). Participants exercised at 50% of maximal oxygen consumption for 60 min with 5 min of rest interspersed every 20 min. PBMCs were isolated pre-exercise, immediately postexercise and 4 h after exercise recovery. Additional PBMCs were incubated for 24 h and either exposed to bafilomycin, rapamycin with bafilomycin (RAPA), or no treatment with vehicle (dimethyl sulfoxide). Proteins and mRNA were analyzed via western blot and quantitative real-time polymerase chain reaction, respectively. Results: Exercise increased autophagy immediately postexercise and recovered 4 h after exercise in control participants but not in participants with prediabetes. Autophagy increased in PBMCs from people with prediabetes and control participants after RAPA treatment; however, a significantly impaired autophagic response was observed in people with prediabetes when compared with control subjects. Conclusions: Our results indicate an impairment in autophagic flux in PBMCs from people with prediabetes when compared with control subjects in response to both exercise and RAPA treatment. Future methods of autophagic upregulation should be investigated to spare malfunctions in autophagy in people with prediabetes. (C) 2019 Canadian Diabetes Association.