Insulin and glucagon in prevention of hypoglycemia during exercise in humans

Abstract

To assess the roles of decrements in insulin and increments in glucagon in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal young men were studied during somatostatin infusions with insulin and glucagon infused to 1) hold insulin and glucagon levels constant, 2) decrease insulin, 3) increase glucagon, and 4) decrease insulin and increase glucagon during exercise. In contrast to a comparison study (saline infusion), when insulin and glucagon were held constant, glucose production did not increase and plasma glucose decreased from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.001) initially during exercise. Notably, plasma glucose then plateaued and was 3.3 +/- 0.2 mmol/l at the end of exercise. This decrease was at most only delayed when either insulin was decreased or glucagon was increased independently. However, when insulin was decreased and glucagon was increased simultaneously, there was an initial increase in glucose production, and the glucose level was 4.5 +/- 0.2 mmol/l at 60 min, a value not different from that in the comparison study. Thus we conclude that both decrements in insulin and increments in glucagon play important roles in the prevention of hypoglycemia during exercise and do so by signaling increments in glucose production. However, since hypoglycemia did not develop during exercise when changes in insulin and glucagon were prevented, an additional counterregulatory factor, such as epinephrine, must be involved in the prevention of hypoglycemia during exercise, at least when the primary factors, insulin and glucagon, are inoperative.

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

“…Therefore, the parallel reduction in hepatic glycogen content between groups despite the obvious differences in the glucagon/insulin ratio suggests that other factors are important for the regulation of hepatic glucose output during exercise performed in the postprandial state in patients with type 1 diabetes. It is plausible that a preserved exercise-induced increase in circulating catecholamines rather than the glucagon response enabled continuous substrate mobilisation from the liver in this patient cohort [14,30,[36][37][38]. It is known that pre-exercise hypoglycaemia is associated with blunted counter-regulation and impaired hepatic glycogenolysis [23,39].…”

“…Third, changes in liver glycogen content during exercise were similar in patients with type 1 diabetes and in controls despite the higher relative systemic hyperinsulinaemia (threefold) present in the former compared with the latter group. Insulin, glucagon and catecholamines respond in a hierarchical fashion to regulate hepatic glucose output and prevent exercise-induced hypoglycaemia [14,[30][31][32]. In non-diabetic individuals a fall in serum insulin concentration and an increase in glucagon occur during exercise.…”

“…Second, in addition to the fall in insulin, a rise in glucagon is required for the full increment in hepatic glucose output [13]. Prevention of this physiological response results in attenuation of hepatic glucose output [14]. It has also been suggested that the increased risk of hypoglycaemia in patients with type 1 diabetes could be due to impaired stimulation of hepatic glucose output in response to glucagon [15].…”

The Effect Of Sodium And Carbohydrate In A Rehydration Food On Subsequent Exercise Performance

“…During moderate intensity exercise, hepatic glucose output is regulated by alterations in glucagons, insulin and epinephrine. During moderate intensity exercise, both decrements in insulin and increments in glucagon prevented exercise-induced hypoglycemia by signaling glucose production in the liver (22). Epinephrine is also a factor influencing hepatic glucose output.…”

“…Epinephrine is also a factor influencing hepatic glucose output. Epinephrine may be involved in the prevention of hypoglycemia during exercise, at least when the changes in insulin and glucagon do not occur (22). In contrast, during high-intensity exercise, catecholamines, in particular epinephrine, plays an important role in mediating hepatic glucose output (23).…”