Impact of Polymorphism in the beta(2)-Receptor Gene on the Metabolic Response to Epinephrine After Repeated Hypoglycemia

The beta(2)-receptor mediates the metabolic response to epinephrine. This study investigates the impact of the beta(2)-receptor gene (ADRB2) polymorphism Gly16Arg on the metabolic response to epinephrine before and after repetitive hypoglycemia. Twenty-five healthy men 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): D1(pre) and D4(post) with epinephrine 0.06 mu g kg(-1).min(-1) infusion and D2(hypo1-2) and D3(hypo3) with three periods of hypoglycemia by an insulin-glucose clamp. At D1pre, the insulin (mean +/- SEM of area under the curve 44 +/- 8 vs. 93 +/- 13 pmol . L-1 h; P = 0.0051), glycerol (79 +/- 12 vs. 115 +/- 14 mu mol . L-1 h; P = 0.041), and free fatty acid (724 +/- 96 vs. 1,113 +/- 140 mu mol . L-1 h; P = 0.033) responses to epinephrine were decreased in AA participants compared with GG participants but without a difference in glucose response. There were no differences in response to epinephrine between genotype groups after repetitive hypoglycemia at D4post. The metabolic substrate response to epinephrine was decreased in AA participants compared with GG participants but without a difference between genotype groups after repetitive hypoglycemia.