In support of a physiological role of this response, it is noteworthy that endogenous GH stimulated by either ghrelin or exercise also induces pSTAT5 in human skeletal muscle in vivo. It is likely that the signaling response to an exogenous GH bolus is influenced by the participant��s pre-study exposure to GH. Recognized determinants of GH secretion and action in human subjects include age, gender, body composition and physical fitness. We observed a positive correlation between the participants TBF and GH signaling, whereas both LBM and VO2- max/body weight correlated negatively with GH signaling. Fat mass is known to be inversely related to GH secretion, whereas the opposite is true for LBM and VO2- max. To reconcile these observations we speculate that pre-study GH levels may suppress GH signaling induced by an exogenous GH bolus. This hypothesis obviously needs to be experimentally addressed in future studies which also should account for other determinants of GH secretion such as gender and age. The GH-induced activation of STAT5 was unaffected by a concomitant oral glucose load, which is in accord with observations made during a hyperinsulinemic glucose clamp. It has previously been reported that prolonged but not short-term insulin pretreatment inhibits GH signaling via the GHR/JAK2/STAT5B pathway in rat hepatoma cells. Conversely, rapid tyrosine phosphorylation of STAT5 by insulin has been recorded in a perfused rat liver model. Whether these discrepancies reflect tissue-specific or speciesspecific differences remain uncertain, but at present there is no evidence to support that insulin interacts with GH signaling in human muscle or fat in vivo. We observed that insulin signaling proteins in human skeletal muscle in vivo are activated in a distinct PF-05089771 temporal pattern within 30 min after an OGTT. The serial measurements of insulin signaling activity during the OGTT allow examination of temporal physiological Src Inhibitor-1 changes that may not be detected during a glucose clamp. Muscle glucose uptake is difficult to quantify directly during an OGTT.