Altitude and beta-blockade augment glucose utilization during submaximal exercise

Abstract

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.

Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high-altitude deer mice

“…However, empirical evidence in support of this hypothesis is based almost exclusively on studies of humans. Acclimation to hypoxia has been shown to increase carbohydrate utilization in some studies of human lowlanders and in some nonhuman animals (11,12,46,47), but not in others (48,49). In contrast, both Sherpas and Andean Quechuas show evidence for enhanced cardiac glucose uptake at the tissue level (50), and in Sherpas, the decreased ratio of phosphocreatine to ATP in cardiac myocytes suggests a greater reliance on glucose for ATP production (51).…”

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m

“…Lowlanders acutely exposed to high altitude showed a shift toward increased blood glucose utilization relative to normoxic conditions (5,28). After 3 wk of acclimatization, reliance on blood glucose increased even further (5) or decreased (28).…”

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers

“…The acute exposure to reduced partial pressure of oxygen at HA decreases arterial oxygen saturation, stimulates the sympathoadrenal system, and provokes shifts in substrate metabolism (2)(3)(4)(5). Indeed, the response to HA in terms of energy utilization has been deeply investigated (2,(6)(7)(8)(9)(10)(11) but data about endocrine adaptations are scanty and discrepant, likely reflecting different experimental models and wide relative ranges of altitudes, and generally investigating the short-term endocrine response only.…”