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Subcellular localization of glucose transporter 4 in the hypothalamic arcuate nucleus of ob/ob mice under basal conditions
- Source :
- Brain Research. 1049:34-42
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- 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 Ser307 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 Ser307 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.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
Monosaccharide Transport Proteins
Glucose uptake
Mice, Obese
Muscle Proteins
White adipose tissue
Protein Serine-Threonine Kinases
Mice
Arcuate nucleus
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Insulin
Tissue Distribution
Obesity
Molecular Biology
Protein kinase B
Neurons
Glucose Transporter Type 4
biology
General Neuroscience
Cell Membrane
Arcuate Nucleus of Hypothalamus
Glucose transporter
nutritional and metabolic diseases
Phosphoproteins
Immunohistochemistry
Receptor, Insulin
Mice, Inbred C57BL
Insulin receptor
Endocrinology
Hypothalamus
Body Composition
Insulin Receptor Substrate Proteins
biology.protein
Neurology (clinical)
Proto-Oncogene Proteins c-akt
hormones, hormone substitutes, and hormone antagonists
GLUT4
Signal Transduction
Subcellular Fractions
Developmental Biology
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1049
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....6ab54b89b090cca1434b411be22dcbe5