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Publication : Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions.

First Author  Komori T Year  2005
Journal  Brain Res Volume  1049
Issue  1 Pages  34-42
PubMed ID  15925330 Mgi Jnum  J:99184
Mgi Id  MGI:3581454 Doi  10.1016/j.brainres.2005.04.079
Citation  Komori T, et al. (2005) Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions. Brain Res 1049(1):34-42
abstractText  Glucose transporter (GLUT) 4 plays an important role in insulin-induced glucose uptake in skeletal muscle and white adipose tissue. Although GLUT4 is abundant in the hypothalamus as well as in these peripheral tissues, little is known about the role of GLUT4 in the hypothalamus. In this study, we examined the subcellular localization of GLUT4 and the activation of insulin signaling pathways in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions. The expression of GLUT4 in the arcuate nucleus of ob/ob mice was higher than that in lean mice. Interestingly, GLUT4 on the plasma membrane increased significantly in neurons of the arcuate nucleus of ob/ob mice when compared to that in lean mice. Because serum insulin levels of ob/ob mice were very high, we hypothesized that insulin strongly stimulates GLUT4 translocation in the arcuate nucleus of ob/ob mice. Unexpectedly, tyrosine phosphorylation of IR and insulin receptor substrate-1 (IRS-1) was faint in the hypothalamus of lean and ob/ob mice. In addition, phosphorylation of IRS-1 at Ser(307) in the hypothalamus of ob/ob mice was higher when compared to that in lean mice, suggesting that insulin signaling is impaired by phosphorylation of IRS-1 at Ser(307) in the hypothalamus of ob/ob mice. However, serine phosphorylation of Akt in the arcuate nucleus of ob/ob mice increased significantly when compared to that in lean mice. Furthermore, the expression of brain-derived neurotrophic factor, an activator of PI3K-Akt pathway in neurons, increased significantly in the ventromedial hypothalamus of ob/ob mice. We discuss the possibility of novel pathways which induce the translocation of GLUT4 in the arcuate nucleus of ob/ob mice.
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