Document Detail

Targeting the association of calgranulin B (S100A9) with insulin resistance and type 2 diabetes.
MedLine Citation:
PMID:  23207880     Owner:  NLM     Status:  MEDLINE    
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.
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-04
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  91     ISSN:  1432-1440     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-29     Completed Date:  2013-09-13     Revised Date:  2013-10-23    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  523-34     Citation Subset:  IM    
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03/0010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
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MeSH Terms
Adipose Tissue / drug effects,  metabolism
Calgranulin B / blood,  genetics*,  metabolism
Diabetes Mellitus, Type 2 / blood,  genetics*,  metabolism
Disease Models, Animal
Gene Expression Regulation / drug effects
Genetic Association Studies
Insulin Resistance / genetics*
Metformin / pharmacology
Middle Aged
Muscles / drug effects,  metabolism
Polymorphism, Single Nucleotide
Reg. No./Substance:
0/Calgranulin B; 657-24-9/Metformin
Erratum In:
J Mol Med (Berl). 2013 Apr;91(4):535
Note: Serino, Matteo [added]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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