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

The physiological role of the adrenergic beta-3 receptor is poorly understood in man but the Trp64Arg mutation of the receptor gene has been related to the insulin resistance syndrome, an earlier onset of diabetes and rapid weight gain. This study set out to examine the effects of the mutation on glycaemic responses after an oral glucose tolerance test.

A standard oral glucose tolerance test (75 g glucose) was performed in 196 dizygotic twins. Serum insulin and glucose responses were measured at 0, 30 and 120 min.

In the twins discordant for the mutation (21 pairs), no effects of the mutation were found on the plasma glucose responses. The insulin response given as incremental area under curve (iAUC) (median 13.8 (25-75th percentile 9.3-21.0) vs. 23.3 (14.2-29.2) mmol x l(-1) x min, P<0.021) and the insulinogenic index ((insulin30min - insulin0min)/ (glucose30min - glucose0min)), 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 results were confirmed when using non-paired statistics on all subjects.

It was concluded that the adrenergic beta-3 receptor, in addition to its already known effects, may be involved in the regulation of insulin secretion and that patients with the Trp64Arg mutation present an impaired insulin secretion.