High uric acid directly inhibits insulin signalling and induces insulin resistance
| Autor: | Jidong Cheng, Ichiro Hisatome, Zhi Li, Yaqiu Hu, Tetsuya Yamamoto, Yongneng Zhang, Huier Yuan, Yuzhang Zhu, Chaohuan Luo, Yinfeng Luo, Tianliang Huang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Biophysics Hyperuricemia Biology Biochemistry Antioxidants Impaired glucose tolerance chemistry.chemical_compound Mice Insulin resistance Internal medicine Glucose Intolerance medicine Animals Humans Insulin Phosphorylation Molecular Biology Protein kinase B Glucose tolerance test medicine.diagnostic_test Insulin tolerance test Cell Biology Hep G2 Cells medicine.disease IRS1 Acetylcysteine Uric Acid Mice Inbred C57BL Disease Models Animal Oxidative Stress Endocrinology chemistry Insulin Receptor Substrate Proteins Uric acid Insulin Resistance Reactive Oxygen Species Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 447(4) |
| ISSN: | 1090-2104 |
| Popis: | Background and aim Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice. Methods An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signalling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment. Results Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells. Conclusion This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro . Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance. |
| Databáze: | OpenAIRE |
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