Targeting the association of calgranulin B (S100A9) with insulin resistance and type 2 diabetes
| العنوان: | Targeting the association of calgranulin B (S100A9) with insulin resistance and type 2 diabetes |
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| المؤلفون: | Francisco J, Ortega, Josep M, Mercader, José M, Moreno-Navarrete, Mónica, Sabater, Neus, Pueyo, Sergio, Valdés, Bartomeu, Ruiz, Elodie, Luche, Matteo, Serino, Deborah, Naon, Wifredo, Ricart, Patricia, Botas, Elias, Delgado, Remy, Burcelin, Gema, Frühbeck, Fatima, Bosch, Gertrude, Mingrone, Antonio, Zorzano, José M, Fernández-Real |
| المصدر: | Journal of Molecular Medicine. 91:523-534 |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Genotype, Adipose tissue, Inflammation, Type 2 diabetes, Biology, Polymorphism, Single Nucleotide, S100A9, Impaired glucose tolerance, Mice, chemistry.chemical_compound, Insulin resistance, Diabetes mellitus, Internal medicine, Drug Discovery, medicine, Animals, Calgranulin B, Humans, Alleles, Genetic Association Studies, Genetics (clinical), Aged, Muscles, Middle Aged, medicine.disease, Metformin, Diet, Disease Models, Animal, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Gene Expression Regulation, chemistry, Molecular Medicine, Female, Glycated hemoglobin, Insulin Resistance, medicine.symptom |
| الوصف: | Calgranulin B (S100A9) was recognized as a candidate type 2 diabetes (T2D) gene in the genomic profiling of muscle from a rodent model of T2D and identifying the human orthologs of genes localized in T2D susceptibility regions. Circulating and S100A9 expressions in muscle and adipose tissue, isolated fat cells, and mouse models were evaluated. A common 5'-upstream single-nucleotide polymorphism (SNP; rs3014866) for S100A9 was analyzed, as well as the effects of weight loss and treatments in vitro with recombinant S100A9. S100a9 expression was increased in muscle of diabetic mice (1.6-fold, p = 0.002), and in muscle from subjects with impaired glucose tolerance (∼4-fold, p = 0.028; n = 34). The rs3014866 SNP was associated with circulating S100A9 and the risk of T2D, having TT carriers at 28 % (p = 0.03) lower risk (n = 1,450). Indeed, increased circulating S100A9 (∼4-fold, p = 0.03; n = 206) and subcutaneous (2-fold, p = 0.01) and omental (1.4-fold, p = 0.04) S100A9 gene expressions (n = 83) in TT carriers run in parallel to decreased fasting glucose and glycated hemoglobin. Accordingly, metformin led to increased S100A9 mRNA in ex vivo-treated adipose tissue explants (n = 5/treatment). Otherwise, obese subjects showed a compensatory increase in circulating and S100A9 expressions in adipose (n = 126), as further demonstrated by decreased levels after diet- (-34 %, p = 0.002; n = 20) and surgery-induced (-58 %, p = 0.02; n = 8) weight loss. Lipopolysaccharide led to increased S100A9 in adipose from mice (n = 5/treatment) while recombinant S100A9 downregulated inflammation in adipocytes (n = 3/treatment). Current findings support the strategy of testing differentially expressed genes in mice and human orthologs associated with T2D. The increased S100A9 reported for obesity and insulin resistance may be envisioned as a compensatory mechanism for inflammation. |
| تدمد: | 1432-1440 0946-2716 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d8a53fae67a8d49b2c63757311c98ba https://doi.org/10.1007/s00109-012-0979-8 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....0d8a53fae67a8d49b2c63757311c98ba |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14321440 09462716 |
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