期刊
GROWTH HORMONE & IGF RESEARCH
卷 20, 期 3, 页码 212-219出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.ghir.2010.02.001
关键词
IGF-I; Adipocytes; 3T3-L1 adipocyte; ROS; Insulin resistance; IRS-1
资金
- Japanese Ministry of Education Science, Sports and Culture
- Japanese Ministry of Health, Welfare and Labor
- Foundation for Growth Science
- Ministry of Education, Culture, Sports, Science and Technology of Japan
Objective: IGF-I is known to enhance insulin sensitivity in whole body mainly via the IGF-I receptors in muscles. However, the effect of IGF-I on the regulation of insulin sensitivity in the adipose tissue is yet unclear. Insulin sensitivity was found to be higher in the IGF-I receptor-deficient adipocytes than that in wild-type adipocytes, suggesting that IGF-I signaling induces insulin resistance in adipocytes. However, the underlying mechanism has not yet been elucidated. In addition, the effect of superphysiological levels of IGF-I, as is observed in patients with acromegaly, on insulin sensitivity remains unclear. Design: To clarify the role of IGF-I on insulin sensitivity in adipocytes, we determined insulin-induced glucose uptake and IRS-1 status in 3T3-L1 adipocytes treated with IGF-I. Since reactive oxygen species (ROS) are causally related to insulin resistance, we investigated the effect of IGF-I on ROS production to elucidate the molecular mechanism underlying insulin resistance. Results: Preincubation of the adipocytes with IGF-I attenuated insulin-dependent glucose uptake. Interestingly, we found that IGF-I significantly stimulated ROS production. Furthermore, preincubation of adipocytes with an antioxidant, N-acetyl-cysteine (NAC) restored the IGF-I-induced attenuation of insulin-dependent glucose uptake; this indicates that IGF-I induces insulin resistance via ROS. Serine phosphorylation of IRS-1 was strongly induced and the insulin-dependent tyrosine phosphorylation of IRS-1 was suppressed by preincubating the adipocytes with IGF-I. Further, NAC restored these changes induced by IGF-I on both senile and tyrosine phosphorylation of IRS-1. Conclusions: These data indicate that IGF-I inhibited insulin activity in the 3T3-L1 adipocytes via ROS production, which affects IRS-1 phosphorylation status. (C) 2010 Elsevier Ltd. All rights reserved.
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