Adrenergic modulation of potassium metabolism during exercise in normal and diabetic humans

The effect of acute and chronic β- and α-adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% VO₂(max)) was investigated in control and insulin-dependent diabetic subjects. In protocol I, subjects were studied during 1) exercise alone, 2) exercise plus intravenous propranolol, and 3) exercise plus intravenous phentolamine. In both the control and diabetic groups, exercise alone produced a modest increase in the plasma potassium concentration (0.31 ± 0.06 meq/l), while propranolol exacerbated this hyperkalemic response. In contrast, the increment in plasma potassium during phentolamine was similar to exercise alone in normals but was 26% (P < 0.05) lower in the diabetic group. In protocol II, the effect of chronic (5 days) β-adrenergic blockade on potassium homeostasis was examined. Subjects participated in three studies: 1) exercise alone, 2) exercise plus propranolol (β₁/β₂-antagonist), and 3) exercise plus metoprolol (β₁ antagonist). In the nondiabetic group, both propranolol and metoprolol were associated with a 40% greater increase in potassium compared with exercise alone. In the diabetic group, propranolol, but not metoprolol, was associated with a deterioration in potassium tolerance. In no study could the alterations in potassium homeostasis be explained by a change in urinary potassium excretion. In summary, 1) α-adrenergic blockade ameliorates exercise-induced hyperkalemia in diabetic but not in control subjects, 2) nonspecific β-adrenergic blockade causes a greater increment in potassium when compared with exercise alone, and 3) specific β₁-adrenergic blockade exacerbates exercise-induced hyperkalemia in control, but not in diabetic subjects. These results indicate that both α- and β-adrenergic regulation of extrarenal potassium metabolism is altered in insulin-dependent diabetes mellitus.