β-Adrenoceptor regulation in insulin-dependent diabetes mellitus

Abstract

The study was performed to determine whether the regulation of mononuclear leukocyte β-adrenergic receptors and responses was changed in insulin-dependent diabetes mellitus (IDDM). The concentrations of noradrenaline, the (3-adrenoceptor densities, basal cAMP levels and maximal isoprenaline-induced cAMP responses were the same in the diabetic and healthy subjects. After isoprenaline-promoted receptor internalization and uncoupling, the receptor densities and the responsiveness did not differ. In the control group, a highly significant correlation existed between the number of β-adrenoceptors and maximal isoprenaline responses, before (r=0-99, p<0-01) and after (r=0-96, p<0-01) receptor internalization and uncoupling. This correlation between receptor densities and responses was not present in the IDDM group, which also showed elevated levels of plasma adrenaline. This study demonstrates that IDDM subjects have an unaltered mechanism of agonist-promoted β-adreno-ceptor internalization, but indicates a partial dysfunction of the β-adrenoceptor-coupling to adenylate cyclase.

Key Words:

• catecholamines
• β-adrenoceptors
• cAMP
• receptor regulation and coupling