The Trp64Arg mutation of the adrenergic beta-3 receptor gene impairs insulin secretion: a twin study

Aims The physiological role of the adrenergic beta-3 receptor is poorly und erstood in man but the Trp64Arg mutation of the receptor gene has been rela ted to the insulin resistance syndrome, an earlier onset of diabetes and ra pid weight gain. This study set out to examine the effects of the mutation on glycaemic responses after an oral glucose tolerance test. Methods A standard oral glucose tolerance test (75g glucose) was performed in 196 dizygotic twins. Serum insulin and glucose responses were measured a t 0, 30 and 120 min. Results In the twins discordant for the mutation (21 pairs), no effects of the mutation were found on the plasma glucose responses. The insulin respon se given as incremental area under curve (iAUC) (median 13.8 (25-75th perce ntile 9.3-21.0) vs. 23.3 (14.2-29.2) mmol.l(-1).min, P < 0.021) and the ins ulinogenic index ((insulin(30min) - insulin(0min))/(glucose(30min) - glucos e(0min))), a measure of the insulin secretory capacity (44 (34-58) vs. 75 ( 42-124), P < 0.006), were considerably lower in the variant type. The resul ts were confirmed when using non-paired statistics on all subjects. Conclusion It was concluded that the adrenergic beta-3 receptor, in additio n to its already known effects, may be involved in the regulation of insuli n secretion and that patients with the Trp64Arg mutation present an impaire d insulin secretion.