We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Monoclonal antibody to six transmembrane epithelial antigen of prostate-4 influences insulin sensitivity by attenuating phosphorylation of P13K (P85) and Akt: Possible mitochondrial mechanism.
- Authors
Da-ni Qin; Jin-gai Zhu; Chen-bo Ji; Chunmei Shi; Chun-zhao Kou; Guan-zhong Zhu; Chun-mei Zhang; Yan-ping Wang; Yu-hui Ni; Xi-rong Guo
- Abstract
We examined the effects of anti-six-transmembrane epithelial antigen of the prostate-4 (STEAP4) antibodies on glucose transport in mature adipocytes and determined the mechanism of insulin resistance in obesity. Western blotting was performed to determine STEAP4 expression, to assess translocation of insulin-sensitive glucose transporter 4 (GLUT4), and to measure phosphorylation and total protein content of insulin-signaling proteins. Confocal laser microscopy and flow cytometry were used to detect intracellular reactive oxygen species (ROS) and fluctuations in mitochondrial membrane potential (ΔΨ). ATP production was measured by using a luciferase-based luminescence assay kit. After the application of anti-STEAP4 antibodies at 0.002 mg/mL, adipocytes exhibited reduced insulin-stimulated glucose transport by attenuating the phosphorylation of IRS-1, PI3K (p85), and Akt. The antibodies also potentially increase the level of ROS and decrease cellular ATP production and ΔΨ. In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance. These observations highlight the potential role of STEAP4 in glucose homeostasis and possibly in the pathophysiology of type 2 diabetes related to obesity and may provide new insights into the mechanisms of insulin resistance in obesity.
- Subjects
ANTIGENS; IMMUNOGLOBULINS; OBESITY; INSULIN receptors; PHOSPHORYLATION; REACTIVE oxygen species; HOMEOSTASIS; PATHOLOGICAL physiology
- Publication
Journal of Bioenergetics & Biomembranes, 2011, Vol 43, Issue 3, p247
- ISSN
0145-479X
- Publication type
Article
- DOI
10.1007/s10863-011-9360-9