Catecholamines in prevention of hypoglycemia during exercise in humans

Abstract

To assess the role of catecholamines in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal humans were studied with combined alpha- and beta-adrenergic blockade and with adrenergic blockade while changes in insulin and glucagon were prevented with the islet clamp technique (somatostatin infusion with insulin and glucagon infused at fixed rates). The results were compared with those from an islet clamp alone study. In contrast to a comparison study (saline infusion), adrenergic blockade resulted in a small initial decrease in plasma glucose during exercise, from 5.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l (P less than 0.01), but the level then plateaued. There was a substantial exercise-associated decrement in plasma glucose when insulin and glucagon were held constant, i.e., from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.0001), but the level again plateaued. However, when insulin and glucagon were held constant and catecholamine actions were blocked simultaneously, progressive hypoglycemia, to 2.6 +/- 0.6 mmol/l (P less than 0.001), developed during exercise. Hypoglycemia was the result of an absent increase in glucose production and an exaggerated initial increase in glucose utilization. Thus we conclude that sympathochromaffin activation plays a minor role when insulin and glucagon are operative, but a catecholamine, probably epinephrine, becomes critical to the prevention of hypoglycemia during exercise when changes in insulin and glucagon do not occur.

Prevention of Overt Hypoglycemia During Exercise

“…Marker et al (12) proposed that epinephrine is a mediator of R a under mildly hypoglycemic exercise conditions. This contention was based on a greater fall in plasma glucose during exercise in the presence of PC/HAB compared with PC.…”

“…However, studies designed to assess the role of sympathetic drive to the liver in the stimulation of R a , using chronic denervation (8), local hepatic adrenergic blockade (9,10), and liver transplant patients (presumably free of sympathetic innervation to the liver) (11), have been uniformly negative. Nevertheless, studies performed in humans using the pancreatic clamp technique and combined ␣-and ␤-adrenergic blockade suggest that epinephrine may prevent overt hypoglycemia during moderate exercise (12). A fall in the level of glycemia has also been suggested as a stimulus to R a via autoregulation at the liver (13).…”

Fatty acid kinetic responses to exercise. Effects of obesity, body fat distribution, and energy-restricted diet.

“…The mechanism(s) for the increased FFA response to exercise following weight loss and the smaller incremental lipolytic responses seen in upper body obese women cannot be established from this study. Insulin (37) and catecholamines (2,4) are the major regulators ofadipose tissue lipolysis, and changes may have occurred in both regulatory systems with weight loss, which may enhance the lipolytic response to exercise. For example, plasma insulin concentrations were slightly lower in both groups throughout the post-weight-loss study, which could allow a greater lipolytic response.…”

“…Free fatty acid release increases during exercise, providing an important circulating fuel for muscle. Catecholamines are thought to play a critical role in assuring normal exercise FFA availability (4). Ifthe lipolytic response to catecholamines dur-ing exercise is subnormal in upper body obesity, loss of fat might be impaired and exercise capacity limited.…”

Olympic diabetes

“…In health, blood glucose concentration is kept within a narrow range during exercise, with muscle glucose utilisation closely balanced by hepatic and renal gluconeogenesis. The stimulation of gluconeogenesis, induced by exercise and falling blood glucose, is mediated by rapidly increasing levels of glucagon, 12-14 the catecholamines [15][16][17] and growth hormone. 18 Low levels of insulin, controlling hepatic glucose output, regulate glucose production.…”