Pioglitazone does not enhance exogenous glucose oxidation or metabolic clearance rate during aerobic exercise in men under acute high altitude exposure

Abstract

Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer prior to acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of Pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared to placebo (PLA) during aerobic exercise at HA. Using a randomized, crossover design, native lowlanders (n=7 males, mean±SD, age: 23±6 yr, body mass: 84±11 kg) consumed 145 g (1.8 g/min) glucose while performing 80-min of steady-state (1.43±0.16 V̇O₂ L/min) treadmill exercise at HA (460 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes (¹³C-glucose and [6,6-²H₂]-glucose). Exogenous glucose oxidation was not different between PIO (0.31±0.03 g/min) and PLA (0.32±0.09 g/min). Total carbohydrate oxidation (PIO: 1.65±0.22 g/min, PLA: 1.68±0.32 g/min) or fat oxidation (PIO: 0.10±0.0.08 g/min, PLA: 0.09±0.07 g/min) were not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46±0.27, PLA: 2.43±0.27 mg/kg/min), disappearance (PIO: 2.19±0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63±0.37, PLA: 1.73±0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.