Phosphorylation status of fetuin-A is critical for inhibition of insulin action and is correlated with obesity and insulin resistance
| Autor: | Laurel A. Littlefield, Suresh T. Mathews, Vishal Kothari, Rebecca A. Ludvigsen, Mary M. Nickles, Peter W. Grandjean, A. Jack Mahurin, Robert L. Bowers, Teayoun Kim, Hilal Zaid, Xiaoming He, James B. Papizan, Guang Ren, Phillip J. Bilan, Carl K. Okerberg, Felipe Araya-Ramirez |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty alpha-2-HS-Glycoprotein Physiology Endocrinology Diabetes and Metabolism Glucose uptake medicine.medical_treatment 030209 endocrinology & metabolism CHO Cells Type 2 diabetes Insulin Antagonists Mice 03 medical and health sciences Cricetulus 0302 clinical medicine Insulin resistance 3T3-L1 Cells Cricetinae Physiology (medical) Internal medicine medicine Animals Humans Insulin Obesity Phosphorylation Cells Cultured Aged biology business.industry Middle Aged medicine.disease Fetuin Rats Rats Zucker Mice Inbred C57BL Insulin receptor 030104 developmental biology Endocrinology biology.protein Insulin Resistance business Protein Kinases |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 317:E250-E260 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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