Stimulation of 2-Deoxy-D-Glucose Uptake in Rat Thymocytes in Vitro by Physiological Concentrations of Triiodothyronine, Insulin, or Epinephrine*

The effects of T3, epinephrine, and insulin, both alone and in varying combinations, on the uptake of 2-deoxy-Dglucose (2-DG) by rat thymocytes in vitro was examined. Each of the three hormones was demonstrated to induce a dose-related increase in 2-DG uptake, and the lowest concentrations at which a significant effect was evident were 1 nM for T3, 1 μM for epinephrine, and 10 nM for insulin. Although supraphysiological concentrations were required when the hormones acted alone, each hormone could be shown to have a significant stimulatory effect at a physiological concentration when it was added together with both of the other hormones. Minimum effective concentrations of each of the three hormones when added with the other two were 5 pM for T3, 10 nM for epinephrine, and 0.1 nM for insulin. Similar results with respect to the effects of physiological concentrations of T3 were observed in experiments with 3-O-methylglucose, which traverses the sae transport mechanism as 2-DG but, unlike 2-DG, does not undergo phosphorylation. This suggests that physiological concentrations of T3 under these conditions act to increase sugar transport. Other experiments revealed that the stimulatory effects on 2-DG uptake elicited by the individual and the combined hormones were independent of new protein synthesis. Two conclusions are drawn from these findings. First, with respect to the stimulatory action of T3 on the transport of sugars that we have previously reported, the data are consonant with the interpretation that the effect has physiological relevance and is mediated at an extranuclear, probably a plasma membrane, site. Second, the data emphasize the likelihood that the inherent sensitivity of some biological responses to a given agent, whentested in vitro, is not apparent because of the absence of other factors that support or enhance the response to the agent in vivo. Consequently, the physiological relevance of an in vitro response should not be dismissed merely because the concentration of the hormone or other agent required to produce that response exceeds its concentration in vivo.