Decreased IRS2 and TIMP3 Expression in Monocytes From Offspring of Type 2 Diabetic Patients Is Correlated With Insulin Resistance and Increased Intima-Media Thickness
| العنوان: | Decreased IRS2 and TIMP3 Expression in Monocytes From Offspring of Type 2 Diabetic Patients Is Correlated With Insulin Resistance and Increased Intima-Media Thickness |
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| المؤلفون: | Davide Lauro, Renato Lauro, Iris Cardolini, Alessio Luzi, Francesca Davato, Rossella Menghini, Massimo Federici, Marina Cardellini, Ottavia Porzio, Stefano Rizza, Paolo Gentileschi, Rossella D'Alfonso, Maria Adelaide Marini, Paolo Sbraccia |
| المصدر: | Diabetes Diabetes; Vol 60 |
| بيانات النشر: | American Diabetes Association, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Complications, Insulin Receptor Substrate Proteins, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Enzyme-Linked Immunosorbent Assay, Type 2 diabetes, 030204 cardiovascular system & hematology, Biology, Carotid Intima-Media Thickness, Polymerase Chain Reaction, Monocytes, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Internal Medicine, medicine, Humans, Insulin, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, 030304 developmental biology, Tissue Inhibitor of Metalloproteinase-3, 0303 health sciences, Settore BIO/12, Glucose clamp technique, Middle Aged, medicine.disease, Atherosclerosis, IRS2, IRS1, Insulin receptor, Endocrinology, Diabetes Mellitus, Type 2, biology.protein, Glucose Clamp Technique, Female, Insulin Resistance |
| الوصف: | OBJECTIVE In humans, it is unclear if insulin resistance at the monocyte level is associated with atherosclerosis in vivo. Here we have studied first-degree relatives of patients with type 2 diabetes to investigate whether a reduction in components of the insulin signal transduction pathways, such as the insulin receptor (InsR) or InsR substrate 1 or 2 (IRS1 or IRS2), or a reduction in genetic modifiers of insulin action, such as the TIMP3/ADAM17 (tissue inhibitor of metalloproteinase 3/A disintegrin and metalloprotease domain 17) pathway, is associated with evidence of atherosclerosis. RESEARCH DESIGN AND METHODS Insulin sensitivity was analyzed through euglycemic-hyperinsulinemic clamp, and subclinical atherosclerosis was analyzed through intimal medial thickness. Monocytes were isolated through magnetic cell sorting, and mRNA and proteins were extracted and analyzed by quantitative PCR and pathscan enzyme-linked immunosorbent assays, respectively. RESULTS In monocyte cells from human subjects with increased risk for diabetes and atherosclerosis, we found that gene expression, protein levels, and tyrosine phosphorylation of IRS2, but not InsR or IRS1, were decreased. TIMP3 was also reduced, along with insulin resistance, resulting in increased ectodomain shedding activity of the metalloprotease ADAM17. CONCLUSIONS Systemic insulin resistance and subclinical atherosclerosis are associated with decreased IRS2 and TIMP3 expression in circulating monocytes. |
| اللغة: | English |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d30296697879a9e2b2d303fdbf585117Test http://europepmc.org/articles/PMC3219931Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d30296697879a9e2b2d303fdbf585117 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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