Investigating how oxidative stress and antioxidant treatment regulate blood sugar levels.

Eligible participants will undergo body composition analysis and resting blood pressure and heart rate will be measured. Participants will then perform a graded exercise test to volitional exhaustion to determine their maximal aerobic capacity and peak power output (Wmax) which will be supervised by an experienced exercise physiologist. After screening, participants will undergo four main testing sessions (exercise, lipid infusion, with and without antioxidant treatment) in a randomised cross-over fashion, with a minimum one-week washout period between sessions. The total intervention (all four testing sessions) is expected to be completed over a period of 4-6 weeks. Upon arrival, a baseline blood sample and resting muscle biopsy sample will be taken and the infusion of the saline or glutathione solution will commence. Concomitant to this infusion (within 15 minutes) participants will undergo either 1 hour of high-intensity interval exercise (including 5 hours of recovery) or 6 hours of intravenous lipid infusion. Participants will remain rested on the hospital bed during the 5-hour post-exercise recovery period and for the duration of the 6-hour lipid infusion session. Insulin action will be measured by a 3-hour euglycaemic hyperinsulinemic clamp conducted during the final 3 hours of lipid infusion and post-exercise recovery period. Venous blood samples will be collected throughout and thigh muscle samples collected at baseline, 1 hour after exercise and lipid infusion, and at the end of the 3-hour insulin clamp. Adherence to the four sessions of the intervention will be monitored by a checklist signed off by the supervising researcher. Exercise protocol. The 1-hour exercise sessions will include a 2-minute warm-up at 50% of maximum estimated sustainable cycling workload (Wmax), followed by 10, 4-minute cycling intervals at 85% Wmax, interspersed with two-minute active recovery periods at 50% Wmax. The exercise will be supervised by an experienced exercise physiologist Lipid and heparin infusion protocol. The lipid infusion session will involve infusion of a commercially available fat emulsion (Intralipid 20%) at a rate of 1.5 mL/min for 6 hours, simultaneously with heparin at 0.4 U/min/kg body weight. Antioxidant infusion protocol. The antioxidant infusion session will involve infusion of L-Glutathione (reduced glutathione) at a rate of 15 mg/min, over 6 hours (5,400mg in total). Placebo infusion protocol. Saline solution (0.9%), which is an inert salty solution, will be infused at a rate of 0.4 ml/min (the same rate as the lipid infusion rate) as a placebo solution in the non-antioxidant control trials and exercise trial. 3-hour euglycaemic hyperinsulinemic clamp protocol. Insulin sensitivity in the main four testing sessions will be measured via a 3-hour euglycaemic hyperinsulinemic euglycaemic insulin clamp. Insulin will be infused at a rate of 40 mU/m2/min. Concurrently, a glucose solution (20% glucose) will be infused at a variable rate to maintain blood glucose concentrations at normal levels (the target is 5 mmol.L-1). This technique is supervised by a medical practitioner and experienced research staff. During the clamp one hand will be warmed to arterialise the blood samples (a safe and easy method for measuring arterial blood). Blood samples (1 ml) will be taken every 5 minutes to monitor glucose which is used to adjust the glucose infusion rate.