Transient Silencing of a Type IV P-Type ATPase, Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that...

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Bibliographic Details
Published in:Journal of nutrition and metabolism 2012-01, Vol.2012 (2012), p.1-9
Main Authors: Dhar, M. S., Biggerstaff, J., Minkin, S. C., Hurst, S. E.
Format: Article
Language:English
Subjects:
2-deoxyglucose
adenosinetriphosphatase
genes
glucose
glucose transporters
insulin
insulin resistance
metabolism
mitogen-activated protein kinase
myotubes
noninsulin-dependent diabetes mellitus
obesity
skeletal muscle
small interfering RNA
transfection
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Summary:Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate that Atp10c regulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.
ISSN:2090-0724
2090-0732
2090-0732
DOI:10.1155/2012/152902