Influence of Tyrphostin AG490 on the expression of diabetes-associated markers in human adipocytes
| Autor: | Rhonda M. Cooper-DeHoff, Abdoreza Davoodi-Semiromi, Martin Wabitsch, Mark A. Atkinson, Azadeh Hassanzadeh, Clive Wasserfall |
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| Rok vydání: | 2012 |
| Předmět: |
Blood Glucose
medicine.medical_specialty medicine.medical_treatment Immunology Peroxisome proliferator-activated receptor Biology Article Rosiglitazone Mice Downregulation and upregulation Mice Inbred NOD Diabetes mellitus Internal medicine Adipocytes Genetics medicine Animals Hypoglycemic Agents Enzyme Inhibitors Janus Kinases NOD mice chemistry.chemical_classification Adiponectin Insulin Protein-Tyrosine Kinases Tyrphostins medicine.disease DNA-Binding Proteins PPAR gamma Diabetes Mellitus Type 1 Glucose Endocrinology chemistry Thiazolidinediones Tyrosine kinase Biomarkers medicine.drug |
| Zdroj: | Immunogenetics. 65:83-90 |
| ISSN: | 1432-1211 0093-7711 |
| Popis: | Tyrosine kinase inhibitors (TKi) hold promise as a treatment for a variety of disorders ranging from those in oncology to diseases thought as immune mediated. Tyrphostin AG490 is a potent Jak-Stat TKi shown effective in the prevention of allograft transplant rejection, experimental autoimmune disease, as well as the treatment of cancer. However, given its ability to modulate this important but pleiotropic intracellular pathway, we thought that it is important to examine its effects on glucose metabolism and expression of major transcription factors and adipokines associated with insulin insensitivity and diabetes. We investigated the metabolic effects of AG490 on glucose levels in vivo using an animal model of diabetes, nonobese diabetic (NOD) mice, and transcription factor expression through assessment of human adipocytes. AG490 treatment of young nondiabetic NOD mice significantly reduced blood glucose levels (p = 0.002). In vitro, treatment of adipocytes with rosiglitazone, an insulin sensitizer that binds to peroxisome proliferator-activated receptor (PPAR) receptors and increases the adipocyte response to insulin, significantly increased the expression of the antidiabetic adipokine adiponectin. Importantly, the combination of rosiglitazone plus Tyrphostin AG490 further increased this effect and was specifically associated with significant upregulation of C-enhanced binding protein (C/EBP) (p |
| Databáze: | OpenAIRE |
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