H1- and H2-receptor Blockade Augments the Glycemic Response to Postexercise Oral Glucose Load

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Following a bout of dynamic exercise, humans experience sustained (90 min) hyperemia in the previously exercised skeletal muscle which is largely mediated by activation of histamine (H1 and H2) receptors. It is well established that skeletal muscle glucose uptake is also enhanced, in an insulin-independent manner, during the first 90 min postexercise. PURPOSE: Our aim was to determine if postexercise hyperemia plays a key role in glucose regulation by enhancing glucose delivery following a bout of exercise. Moreover, we wanted to ascertain if blunting this hyperemia during recovery from exercise would have an adverse effect on blood glucose regulation. Thus, we tested the hypothesis that the glycemic response to oral glucose load (OGTT) following exercise would be higher with H1- and H2-receptor blockade versus control (no blockade). METHODS: Six healthy subjects (20-26 yrs) underwent parallel protocols on two study days, with or without H1- and H2-receptor blockade (fexofenadine and ranitidine). Following 60 min of upright cycling at 60% VO2peak, subjects consumed an oral glucose tolerance beverage (1.0 g/kg). Blood glucose was determined from "arterialized" blood samples (heated hand vein) at 0, 10, 20, 30, 45, 60, 90 and 120 min postexercise. Heart rate, arterial pressure, and femoral blood flow (Doppler ultrasound) were measured pre-exercise and every 15 min postexercise. In addition, six subjects underwent a sham protocol, without exercise, to verify that H1 and H2 blockade did not alter the glycemic response to oral glucose load under resting conditions. RESULTS: During the sham protocol, H1 and H2 blockade did not affect the glycemic response to oral glucose load (P ≥ 0.301). In contrast, H1 and H2 blockade lead to an augmented glycemic response 120 min postexercise, in which blood glucose was 35.6 ± 8.3 mg dl−1 above baseline with H1 and H2 blockade versus 24.1 ± 8.1 mg dl−1 above baseline on the control day (P= 0.002). CONCLUSIONS: These results indicate that the glycemic response to an oral glucose load following exercise is augmented by H1- and H2-receptor blockade. Furthermore, these findings suggest that postexercise H1- and H2 -receptor-mediated skeletal muscle hyperemia can impact glucose delivery in healthy humans. Supported by AHA grant 555623Z and the Evonuk Foundation