Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet
| Autor: | Daniel Konrad, Thomas A. Lutz, J A Pospisilik, Stephan Wueest, L. Van Lommel, Simon M. Schultze, Julia M. Rytka, Sarah Debray, Daniel T. Meier, Frans Schuit, Katleen Lemaire, Helga Ellingsgaard, Simone Boller, O Tschopp, Sabine Rütti, U Malipiero, Jan A. Ehses, Marc Y. Donath, Peter Y. Wielinga, Harald Esterbauer, M. Böni-Schnetzler, Anica Schraenen |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2010 |
| Předmět: |
Blood Glucose
Male Endocrinology Diabetes and Metabolism medicine.medical_treatment 10265 Clinic for Endocrinology and Diabetology Adipose tissue Mice 0302 clinical medicine SX00 SystemsX.ch Insulin-Secreting Cells Insulin Glucose homeostasis Cells Cultured Mice Knockout 2. Zero hunger 0303 health sciences Toll-like receptor Reverse Transcriptase Polymerase Chain Reaction 10081 Institute of Veterinary Physiology 3. Good health 2712 Endocrinology Diabetes and Metabolism medicine.anatomical_structure 10076 Center for Integrative Human Physiology Female medicine.symptom Beta cell medicine.medical_specialty 030209 endocrinology & metabolism Inflammation 610 Medicine & health Biology 03 medical and health sciences Insulin resistance Internal medicine Internal Medicine medicine Animals 030304 developmental biology Analysis of Variance Pancreatic islets Calorimetry Indirect medicine.disease Dietary Fats Toll-Like Receptor 2 Endocrinology SX09 LiverX 10036 Medical Clinic 2724 Internal Medicine 10033 Clinic for Immunology 570 Life sciences biology Insulin Resistance |
| Zdroj: | Diabetologia |
| DOI: | 10.1007/s00125-010-1747-3 |
| Popis: | Inflammation contributes to both insulin resistance and pancreatic beta cell failure in human type 2 diabetes. Toll-like receptors (TLRs) are highly conserved pattern recognition receptors that coordinate the innate inflammatory response to numerous substances, including NEFAs. Here we investigated a potential contribution of TLR2 to the metabolic dysregulation induced by high-fat diet (HFD) feeding in mice. Male and female littermate Tlr2 +/+ and Tlr2 −/− mice were analysed with respect to glucose tolerance, insulin sensitivity, insulin secretion and energy metabolism on chow and HFD. Adipose, liver, muscle and islet pathology and inflammation were examined using molecular approaches. Macrophages and dendritic immune cells, in addition to pancreatic islets were investigated in vitro with respect to NEFA-induced cytokine production. While not showing any differences in glucose homeostasis on chow diet, both male and female Tlr2 −/− mice were protected from the adverse effects of HFD compared with Tlr2 +/+ littermate controls. Female Tlr2 −/− mice showed pronounced improvements in glucose tolerance, insulin sensitivity, and insulin secretion following 20 weeks of HFD feeding. These effects were associated with an increased capacity of Tlr2 −/− mice to preferentially burn fat, combined with reduced tissue inflammation. Bone-marrow-derived dendritic cells and pancreatic islets from Tlr2 −/− mice did not increase IL-1β expression in response to a NEFA mixture, whereas Tlr2 +/+ control tissues did. These data suggest that TLR2 is a molecular link between increased dietary lipid intake and the regulation of glucose homeostasis, via regulation of energy substrate utilisation and tissue inflammation. |
| Databáze: | OpenAIRE |
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