Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tiss...

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Veröffentlicht in:	PloS one Jg. 11; H. 4; S. e0154119
Hauptverfasser:	Amouzou, Cacylde, Breuker, Cyril, Fabre, Odile, Bourret, Annick, Lambert, Karen, Birot, Olivier, Fédou, Christine, Dupuy, Anne-Marie, Cristol, Jean-Paul, Sutra, Thibault, Molinari, Nicolas, Maimoun, Laurent, Mariano-Goulart, Denis, Galtier, Florence, Avignon, Antoine, Stanke-Labesque, Françoise, Mercier, Jacques, Sultan, Ariane, Bisbal, Catherine
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 25.04.2016 Public Library of Science (PLoS)
Schlagworte:	Adipose tissue AKT protein Biology and Life Sciences Blood Glucose - metabolism Body mass Body mass index Body size C-Reactive Protein Case-Control Studies Cell Movement - drug effects Comparative analysis Complications and side effects Cytokines Development and progression Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Diet Female Gene Expression Regulation Glucose Glucose Clamp Technique Homeostasis Humans Infiltration Inflammation Insulin Insulin - administration & dosage Insulin - metabolism Insulin Resistance Interleukin 6 Interleukin-6 - genetics Interleukin-6 - metabolism Kinases Life Sciences Lipids Lipopolysaccharides Macrophages Macrophages - drug effects Macrophages - metabolism Macrophages - pathology Medicine and Health Sciences Middle Aged Muscle, Skeletal - metabolism Muscle, Skeletal - physiopathology Muscles NF-KappaB Inhibitor alpha - genetics NF-KappaB Inhibitor alpha - metabolism Obesity Parameter sensitivity Phosphorylation Physiological aspects Postmenopause - metabolism Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Quality Risk factors Sensitivity Sensitivity analysis Severity of Illness Index Skeletal muscle Subcutaneous Fat - metabolism Subcutaneous Fat - physiopathology Surveys and Questionnaires Tissues France
ISSN:	1932-6203, 1932-6203
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Zusammenfassung:	Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity. We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development. 30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression. Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR. Our results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 Conceived and designed the experiments: AS C. Bisbal. Performed the experiments: CA C. Breuker OF AB KL TS LM OB CF AMD JPC FSL DMG C. Bisbal. Analyzed the data: CA C. Breuker OF NM AS C. Bisbal. Wrote the paper: CA OF AS C. Bisbal. Recruitment of the volunteers: OF AA AS FG JM. Competing Interests: The authors have declared that no competing interests exist. These authors also contributed equally to this work.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0154119