In order to assess the adrenergic contribution to hypoglycemie glucose counterregulation in type | diabetes mellitus and to determine whether the adrenergic contribution is mediated through beta1- or beta2-adrenergic receptors, hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 · min) for 60 min in 11 insulin-dependent diabetic patients (IDDM), 5 with normal plasma glucagon responses and 6 with blunted responses, and also in 7 age-weight-matched nondiabetic subjects. Rates of plasma glucose decrease and postnadir increase, as well as plasma concentrations of free insulin and of counterregulatory hormones, were measured when insulin was infused alone, and when insulin was infused along with propranolol (a beta1- and beta2-adrenergic receptor antagonist) or metoprolol (a selective beta1-antagonist). Postnadir plasma glucose recovery was decreased in IDDM with blunted plasma glucagon responses (21 ± 0.8 µmol. L−1 min−1, P < 0.001), but was normal in patients with normal plasma glucagon responses (30 ± 0.4 versus 33 ± 0.5 μmol · L−1 · min−1 in nondiabetic subjects, P = NS). Postnadir plasma glucose recovery was not affected by either propranolol or metoprolol in normal subjects and in IDDM with normal glucagon responses. However, in IDDM with blunted plasma glucagon responses, postnadir plasma glucose recovery was further decreased by propranolol (14 ± 0.6 µmol. L−1 min1, P < 0.01), but was unaffected by metoprolol (22 ± 0.9 μmol. L 1 min1, P = NS).
These results demonstrate that, as in normal man, adrenergic mechanisms are not essential for normal plasma glucose recovery from hypoglycemia in IDDM with normal plasma glucagon responses. However, in IDDM with blunted plasma glucagon responses, adrenergic mechanisms become important for glucose counterregulation although they do not fully compensate for the blunted plasma glucagon responses. Since propranolol delayed plasma glucose recovery from hypoglycemia in IDDM with blunted glucagon responses but metoprolol had no effect, the adrenergic contribution to glucose counterregulation appears to be mediated through beta2-adrenergic receptors.
