Interleukin-6 regulates pancreatic α-cell mass expansion
| Autor: | François Pattou, Frans Schuit, Thierry Berney, Philippe A. Halban, Jan A. Ehses, Roel Quintens, Marc Y. Donath, Geert A. Martens, Daniel Pipeleers, Julie Kerr-Conte, Helga Ellingsgaard, Eva Hammar, Leentje Van Lommel |
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| Přispěvatelé: | Medical Biochemistry, Department of Bio-engineering Sciences, Pathologic Biochemistry and Physiology, University of Zurich |
| Rok vydání: | 2008 |
| Předmět: |
Protein Precursors/genetics/metabolism
RNA Messenger/genetics Male Endocrinology Diabetes and Metabolism Interleukin-6/metabolism 10265 Clinic for Endocrinology and Diabetology Gene Expression Regulation/drug effects Apoptosis Type 2 diabetes Alpha cell Cell Proliferation/drug effects Mice Insulin-Secreting Cells/cytology Receptors Interleukin-6/genetics Glucagon/genetics/metabolism Insulin-Secreting Cells ddc:576.5 Phosphorylation Insulin-Secreting Cells/cytology/drug effects Mice Knockout Glucose tolerance test Multidisciplinary geography.geographical_feature_category medicine.diagnostic_test Receptors Interleukin-6/genetics/metabolism Glucagon secretion Phosphorylation/drug effects Biological Sciences Islet medicine.anatomical_structure 10076 Center for Integrative Human Physiology Pancreas STAT3 Transcription Factor medicine.medical_specialty RNA Messenger/genetics/metabolism 610 Medicine & health Biology Glucagon Glucagon-Secreting Cells/cytology Internal medicine Diabetes mellitus medicine Animals Humans Feeding Behavior/drug effects Glucagon/genetics RNA Messenger Protein Precursors Rats Wistar Cell Proliferation 1000 Multidisciplinary geography Interleukin-6 Apoptosis/drug effects Protein Precursors/genetics Feeding Behavior Glucose Tolerance Test medicine.disease Dietary Fats Receptors Interleukin-6 Rats Mice Inbred C57BL Dietary Fats/pharmacology Endocrinology Gene Expression Regulation STAT3 Transcription Factor/metabolism Glucagon-Secreting Cells 570 Life sciences biology Glucagon-Secreting Cells/cytology/drug effects |
| Zdroj: | Proceedings of the National Academy of Sciences, Vol. 105, No 35 (2008) pp. 13163-8 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0801059105 |
| Popis: | Interleukin-6 (IL-6) is systemically elevated in obesity and is a predictive factor to develop type 2 diabetes. Pancreatic islet pathology in type 2 diabetes is characterized by reduced β-cell function and mass, an increased proportion of α-cells relative to β-cells, and α-cell dysfunction. Here we show that the α cell is a primary target of IL-6 actions. Beginning with investigating the tissue-specific expression pattern of the IL-6 receptor (IL-6R) in both mice and rats, we find the highest expression of the IL-6R in the endocrine pancreas, with highest expression on the α-cell. The islet IL-6R is functional, and IL-6 acutely regulates both pro-glucagon mRNA and glucagon secretion in mouse and human islets, with no acute effect on insulin secretion. Furthermore, IL-6 stimulates α-cell proliferation, prevents apoptosis due to metabolic stress, and regulates α-cell mass in vivo . Using IL-6 KO mice fed a high-fat diet, we find that IL-6 is necessary for high-fat diet-induced increased α-cell mass, an effect that occurs early in response to diet change. Further, after high-fat diet feeding, IL-6 KO mice without expansion of α-cell mass display decreased fasting glucagon levels. However, despite these α-cell effects, high-fat feeding of IL-6 KO mice results in increased fed glycemia due to impaired insulin secretion, with unchanged insulin sensitivity and similar body weights. Thus, we conclude that IL-6 is necessary for the expansion of pancreatic α-cell mass in response to high-fat diet feeding, and we suggest that this expansion may be needed for functional β-cell compensation to increased metabolic demand. |
| Databáze: | OpenAIRE |
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