Article date: September 1996
By: BRIAN J. LIPWORTH, in Volume 42, Issue 3, pages 291-300
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.
DOI: 10.1046/j.1365-2125.1996.04222.x
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