| Autor: |
Guang Ren, Teayoun Kim, Papizan, James B., Okerberg, Carl K., Kothari, Vishal M., Zaid, Hilal, Bilan, Phillip J., Araya-Ramirez, Felipe, Littlefield, Laurel A., Bowers, Robert L., Mahurin, A. Jack, Nickles, Mary M., Ludvigsen, Rebecca, Xiaoming He, Grandjean, Peter W., Mathews, Suresh T. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Endocrinology & Metabolism; Aug2019, Vol. 317 Issue 2, pE250-E260, 11p |
| Abstrakt: |
Fetuin-A (Fet-A), a hepatokine associated with insulin resistance, obesity, and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin-resistant conditions and its functional significance are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin-resistant Zucker diabetic fatty rats, and in individuals with obesity who are insulin resistant. Unlike serum total fetuin-A, serum phosphofetuin-A was associated with body weight, insulin, and markers of insulin resistance. To characterize potential mechanisms, fetuin-A was purified from Hep3B human hepatoma cells. Hep3B Fet-A was phosphorylated (Ser312) and inhibited insulin-stimulated glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Furthermore, single (Ser312Ala) and double (Ser312Ala + Ser120Ala) phosphorylation-defective Fet-A mutants were without effect on glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Together, our studies demonstrate that phosphorylation status of Fet-A (Ser312) is associated with obesity and insulin resistance and raise the possibility that Fet-A phosphorylation may play a role in regulation of insulin action. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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