Mononuclear Leukocyte β2-Adrenergic Receptors and Adenylate Cyclase Sensitivity in Insulin-dependent Diabetes Mellitus

Patients with insulin-dependent diabetes mellitus (IDDM) have been found to have a heightened hyperglycemic response to epinephrine. To determine if patients with IDDM have increased sensitivity of cellular beta 2-adrenergic receptor-effector systems, we assessed beta 2-adrenergic receptors and adenylate cyclase sensitivities to isoproterenol in partially purified mononuclear leukocyte (MNL) plasma membranes from 10 patients with IDDM (without adrenergic neuropathy) and 10 matched nondiabetic controls. MNL beta 2-adrenergic receptor densities (Bmax = 48 +/- 8 fmol [3H] DHA/mg protein in IDDM, 44 +/- 3 fmol [3H] DHA/mg protein in controls) and binding affinities (apparent KD = 0.3 +/- 0.07 nM in IDDM, 0.3 +/- 0.04 nM in controls) did not differ. Further, MNL adenylate cyclase activities were not significantly different either at baseline (325 +/- 86 pmol/mg protein/15 min in IDDM, 275 +/- 49 pmol/mg protein/15 min in controls) or in response to isoproterenol (842 +/- 229 pmol/mg protein/15 min in IDDM, 608 +/- 86 pmol/mg protein/15 min in controls). Thus, the data do not support the presence of a generalized alteration of beta-adrenergic receptors or adenylate cyclase sensitivity in IDDM. To the extent that MNL beta 2-adrenergic receptors and adenylate cyclase activities reflect those of extravascular catecholamine target cells, these findings suggest that the heightened hyperglycemic response to epinephrine exhibited by patients with IDDM is not due to increased sensitivity of cellular beta 2-adrenergic receptor-effector systems and is best attributed to the altered hormonal milieu of the insulin-deficient state.