Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women |
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| Authors: | Cacylde Amouzou Cyril Breuker Odile Fabre Annick Bourret Karen Lambert Olivier Birot Christine Fédou Anne-Marie Dupuy Jean-Paul Cristol Thibault Sutra Nicolas Molinari Laurent Maimoun Denis Mariano-Goulart Florence Galtier Antoine Avignon Fran?oise Stanke-Labesque Jacques Mercier Ariane Sultan Catherine Bisbal |
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| Institution: | 1PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France;2Centre Hospitalier Régional Universitaire (CHRU) Montpellier, Montpellier, France;3Faculty of Health, York University, York, Ontario, Canada;4University of Grenoble Alpes, INSERM U1042, HP2, Grenoble, CHU Albert Michalon, Grenoble, France;INSERM/UMR 1048, FRANCE |
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| Abstract: | ContextObesity 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.ObjectivesWe 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.Methods30 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.ResultsSystemic 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.ConclusionOur 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. |
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