Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans.

The caffeine-induced impairment of insulin action is commonly attributed to adenosine receptor (AR) antagonism in skeletal muscle. However, epinephrine, a potent inhibitor of insulin actions, is increased after caffeine ingestion. We tested the hypothesis that the insulin antagonistic effects of caffeine are mediated by epinephrine, and not by AR antagonism, in seven healthy men. On four separate occasions, they received 1) dextrose (placebo, PL), 2) 5 mg/kg caffeine (CAF), 3) 80 mg of propranolol (PR), and 4) 5 mg/kg caffeine + 80 mg of propranolol (CAF + PR) before an oral glucose tolerance test (OGTT). Blood glucose was similar among trials before and during the OGTT. Plasma epinephrine was elevated (P < 0.05) in CAF and CAF + PR. Areas under the insulin and C-peptide curves were 42 and 39% greater (P < 0.05), respectively, in CAF than in PL, PR, and CAF + PR. In the presence of propranolol (CAF + PR), these responses were similar to PL and PR. These data suggest that the insulin antagonistic effects of caffeine in vivo are mediated by elevated epinephrine rather than by peripheral AR antagonism.