Peripheral adrenoceptors: the impetus behind glucose dysregulation and insulin resistance.

It is now accepted that several pharmacological drug treatments trigger clinical manifestations of glucose dysregulation, such as hyperglycaemia, glucose intolerance and insulin resistance, in part through poorly understood mechanisms. Persistent sympathoadrenal activation is linked to glucose dysregulation and insulin resistance, both of which significantly increase the risk of emergent endocrinological disorders, including metabolic syndrome and type 2 diabetes mellitus. Through the use of targeted mutagenesis and pharmacological methods, preclinical and clinical research has confirmed physiological glucoregulatory roles for several peripheral α- and β-adrenoceptor subtypes. Adrenoceptor isoforms in the pancreas (α(2A) and β(2) ), skeletal muscle (α(1A) and β(2) ), liver (α(1A & B) and β(2) ) and adipose tissue (α(1A) and β(1 & 3) ) are convincing aetiological targets that account for both immediate and long-lasting alterations in blood glucose homeostasis. Because significant overlap exists between the therapeutic applications of numerous classes of drugs and their associated adverse side-effects, a better understanding of peripheral adrenoceptor-mediated glucose metabolism is thus warranted. Therefore, at the same time as providing a brief review of glucose homeostasis in the periphery, the present review addresses both functional and pathophysiological roles of the mammalian α(1) , α(2) , and β-adrenoceptor isoforms in whole-body glucose turnover. We highlight evidence relating to the clinical use of common adrenergic drugs and their impacts on glucose metabolism.