Impact of polymorphism in the β2-receptor gene on the metabolic response to epinephrine after repeated hypoglycemia

The β2-receptor mediates the metabolic response to epinephrine. This study investigates the impact of the β2-receptor gene (ADRB2) polymorphism Gly16Arg on the metabolic response to epinephrine before and after repetitive hypoglycemia.

Twenty-five healthy male subjects selected according to ADRB2 genotype being homozygous for either Gly16 (GG; n=12) or Arg16 (AA; n=13) participated in 4 trial days (D1-4), D1pre and D4post with epinephrine 0.06 ug kg-1 min-1  infusion, and D2hypo1-2 and D3hypo3 with three periods of hypoglycemia by an insulin-glucose clamp.

At D1pre the insulin (44 ± 8 vs. 93 ± 13 pmol l-1 h; P = 0.0051) and glycerol (79 ± 12 vs. 115 ± 14 μmol l-1 h; P = 0.041) and free fatty acids (FFA) (724 ± 96 vs. 1113 ± 140 μmol l-1 h; P = 0.033) responses (mean ± SEM of area under the curve) to epinephrine were decreased in AA subjects compared to GG subjects but without difference in glucose response. There were no difference in response to epinephrine between genotype groups after repetitive hypoglycemia at D4post.

The metabolic substrate response to epinephrine is decreased in AA subjects compared to GG subjects, but without difference between genotype groups after repetitive hypoglycemia.