To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for > or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.

We tested the hypothesis that exposure to altitude decreases reliance on free fatty acids (FFA) as substrates and increases dependency on blood glucose. Therefore, the effects of exercise, hypobaric hypoxia, and altitude acclimatization on FFA, glycerol and net glucose uptake and release [= 2(leg blood flow)(arteriovenous concentration)] and on fatty acid (FA) consumption by the legs (= 3 x glycerol release + FFA uptake) were measured. Because sympathetic responses have been implicated, we utilized nonspecific beta-blockade and observed responses to exercise, altitude, and altitude acclimatization. We studied six healthy beta-blocked men (beta) and five matched controls (C) during rest and cycle ergometry exercise (88 W) at 49% of sea-level (SL) peak O2 uptake at the same absolute power output on acute altitude exposure (A1; barometric pressure = 430 Torr) and after 3 wk of chronic altitude exposure to 4,300 m (A2). During exercise at SL, FA consumption rates increased (P < 0.05). On arrival at 4,300 m, resting leg FFA uptake and FA consumption rates were not significantly different from those at SL. However, after acclimatization to altitude, at rest leg FA consumption decreased to essentially zero in both C and beta groups. During exercise to altitude after acclimatization, leg FA consumption increased significantly, but values were less than at SL or A1 (P < 0.05), whereas glucose uptake increased relative to SL values. Furthermore, beta-blockade significantly increased glucose uptake relative to control. We conclude that 1) chronic altitude exposure decreases leg FA consumption during rest and exercise; 2) relative to SL FFA uptake decreases while glucose uptake increases during exercise at altitude; and 3) beta-blockade potentiates these effects.