| Autor: |
Peng, Susan, Ciaraldi, Theodore P., Carter, Leslie, Henry, Robert R., Armstrong, Debra, Burke, Paivi, Gasper, Andrea, Herbst, Karen L. |
| Předmět: |
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| Zdroj: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA327-A328, 2p, 2 Graphs |
| Abstrakt: |
Increasing testosterone (T) levels to physiologic range in hypogonadal men with insulin resistance (IR) results in improved insulin sensitivity; increasing T levels to supraphysiologic range, however, induces IR. Since muscle is responsible for >90% total body glucose uptake, we sought to char: acterize glucose uptake (GU) and fatty acid oxidation (Pox) in human muscle cells with increasing androgen concentrations in vitro (0-10µM [0.29290µg/dL]). Fasting biopsies were obtained from the vastus lateralis muscle of 8 obese men (mean BMI 35kg/m²) with low normal free T levels (mean 64pg/mL; normal 34-194pg/mL) and IR by hyperinsulinemic-euglycemic clamp. Muscle cells were grown in culture and differentiated into mature myotubes. Insulin-stimulated GU and Pox were determined after incubation with increasing concentrations oft and dihydrotestosterone (DHT) for 48h. Neither T nor DHT increased GU in the absence of insulin (basal). There was a biphasic effect on GU with increasing concentrations of androgen (Fig A). Compared to no androgen treatment, insulin-stimulated GU was maximally augmented at 0.01µMT (physiologic level) whereas higher androgen concentrations led to a loss of insulin responsiveness. Similar data for GU were found with DHT. Pox increased in a dose-dependent manner beginning at 0.01µM DHT and reached significance at 1.0µM DHT to 25% above control (Fig B). Similar data for Pox were found with T. In summary, insulin-stimulated GU in myotubes is augmented at a physiologic level of androgen (0.01µM); this is the same concentration at which Pox begins to increase. At higher androgen levels, however, insulin action on GU decreases while Pox continues to rise. In conclusion, it has been observed in vivo that T treatment to physiologic range in hypogonadal men with IR improves insulin sensitivity, but higher levels paradoxically induce IR. This result has now been duplicated in human muscle cells in vitro, and the data suggest that a switch from glucose to fatty acid utilization may contribute to the IR observed at supraphysiologic androgen levels. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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