Epinephrine is not critical to prevention of hypoglycemia during exercise in humans

Abstract

We documented stability of plasma glucose concentrations and glucose production and utilization rates, and levels of other metabolic substrates and regulatory factors, during the islet clamp (somatostatin infusion with glucagon and insulin replacement) in the absence of an intervention in five normal humans and further applied this technique to the study of glucoregulation during moderate exercise. Based on previous evidence that sympathochromaffin activation plays a primary role in the prevention of hypoglycemia during exercise, the role of adrenomedullary catecholamines was assessed by exercise (60% of maximum oxygen consumption for 60 min) studies in four bilaterally adrenalectomized, epinephrine-deficient humans under two conditions: control (saline infusion) and islet clamp. Increased glucose utilization and production rates were matched and plasma glucose was unchanged during exercise under both conditions. Thus adrenomedullary catecholamines including epinephrine are not critical to glucoregulation during moderate exercise in humans even when changes in insulin and glucagon are prevented. These findings provide further support for the suggestion that sympathetic neural norepinephrine is the operative catecholamine in the prevention of hypoglycemia during exercise in humans.

Role of the Sympathoadrenal System in Exercise-Induced Inhibition of Insulin Secretion: Effects of Islet Transplantation

“…Data are means ± SE. in previous studies (8)(9)(10). Taken together, these studies indicate that the reduction of insulin levels during exercise is not the result of a 2 -adrenergic inhibition by humoral influences via circulating catecholamines, but that other mechanisms must be involved.…”

“…These processes are facilitated by reduced insulin secretion in the early phase of exercise, together with the stimulating effects of the sympathoadrenal system and pancreatic glucagon (1)(2)(3)(4). Sympathetic influences play a role in the inhibition of insulin secretion (2,(5)(6)(7)(8)(9)(10) by contributions from both the neural and adrenomedullary branches of the sympathetic nervous system. Epinephrine, released from the adrenal medulla, and norepinephrine, released from the sympathetic nerve endings, inhibit insulin release via stimulation of a 2 -adrenergic receptors on the p-cells of the islets of Langerhans (7,11,12).…”

Regulation of Extramuscular Fuel Sources During Exercise

“…This is supported by the demonstration that a-adrenergic blockade prevents the fall in insulin in exercising humans (93,267). The fall in insulin is retained in human subjects who are adrenalectomized for treatment of pheochromocytoma, again suggesting that the sympathetic nerves mediate this hormonal change (125,145). The importance of sympathetic nerves is further supported by the demonstration that insulin levels in long-term islet cell autografted dogs are actually increased by exercise (233).…”

Adrenal medulla and exercise training

“…It has not been possible to detect adrenaline in the plasma of exercising adrenodemedullated rats Scheurink et al 1989). Similarly, in adrenalectomized human subjects who had mineralo-and glucocorticoid hormones replaced the plasma concentrations of adrenaline during exercise have been shown to be less than 10% of what was found in healthy control subjects at the same relative exercise intensity (percentage maximal oxygen uptake, % O 2max ) (Barwich et al 1981;Hoelzer et al 1986). It has been demonstrated that the adrenal medulla is stimulated via sympathetic nerves (Elliott 1913) through the coeliac ganglion, and during exercise in humans injection of local anaesthetic around the coeliac ganglion has been found to reduce the exercise induced increase in arterial plasma adrenaline concentration by up to 90% (Kjñr et al 1993).…”