Effects of insulin and IGF-I on growth hormone- induced STAT5 activation in 3T3-F442A adipocytes

Background: Growth hormone (GH) and insulin signaling pathways are known important regulators of adipose homeostasis. The cross-talk between GH and insulin signaling pathways in mature adipocytes is poorly understood. Methods: In the present study, the impact of insulin on GH- mediated signaling in differentiated 3T3-F442A adipocytes and primary mice adipocytes was examined. Results: Insulin alone did not induce STAT5 tyrosine phosphorylation, but enhanced GH- induced STAT5 activation. This effect was more pronounced when insulin was added 20 min prior to GH treatment. The above results were further confirmed by in vivo study, showing that insulin pretreatment potentiated GH- induced STAT5 tyrosine phosphorylation in visceral adipose tissues of C57/BL6 mice. In addition, our in vitro results showed that IGF-I had similar potentiating effect as insulin on GH- induced STAT5 activation. In vitro, insulin and IGF-I had an additive effect on GH- induced MAPK activation. Conclusion: These results indicate that both insulin and IGF-I specifically potentiated GH mediated STAT5 activation in mature adipose cells. These findings suggest that insulin and GH, usually with antagonistic functions, might act synergistically to regulate some specific functions in mature adipocytes.