Abstract
1An atypical non β1/β2-adrenoceptor (AR) subtype (β3-AR) has been identified which is selectively stimulated by a group of ligands which mediate lipolytic and thermic responses in brown and white adipose tissue.
2Molecular studies have shown that β3-AR in man are mainly expressed in visceral adipocytes, and to a lesser extent in gall-bladder and colon. In vitro studies with β3-AR agonists have shown activity at other sites including skeletal muscle and myocardium.
3Regulation of β3-AR may differ from β1/β2-AR subtypes in that continuous agonist exposure does not result in receptor down-regulation.
4A polymorphism of the human β3-AR gene (Trp64Arg) has been identified which is associated with obesity, insulin resistance and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM). Studies are required to establish whether expression of the mutant gene results in altered metabolic responses to β3-AR stimulation in man.
5There is accumulating evidence to support a therapeutic role of β3-AR agonists in NIDDM because of anti-obesity and anti-diabetic activity, as a consequence of thermogenic effects as well as increased insulin sensitivity and glucose tolerance.
6Selectivity studies with BRL35135 and isoprenaline in humans have demonstrated a β3-AR mediated component to thermogenesis which is dissociated from β1/β2-mediated effects on carbohydrate and fat metabolism. Similar studies have suggested a functional β3-AR mediating cardiac but not airway responses in humans. An evaluation of β3-AR agonists in irritable bowel syndrome may be warranted in view of colonic antimotility properties in vitro.
Keywords: β3-adrenoceptors , lipolysis, thermogenesis
Full Text
The Full Text of this article is available as a PDF (345.8 KB).