C3aR and C5aR1 act as key regulators of human and mouse β-cell function
| Autor: | Patricio Atanes, Ross Hawkes, Shanta J. Persaud, Min Zhao, Inmaculada Ruz-Maldonado, Guo Cai Huang, Attilio Pingitore, Bo Liu, Stefan Amisten |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male endocrine system medicine.medical_specialty Apoptosis Complement receptor Biology 03 medical and health sciences Cellular and Molecular Neuroscience Classical complement pathway Islets of Langerhans Mice 0302 clinical medicine G protein-coupled receptors Internal medicine Insulin-Secreting Cells medicine Glucose homeostasis Animals Humans Anaphylatoxin C3aR Molecular Biology Receptor Anaphylatoxin C5a Cells Cultured beta-Arrestins Pharmacology Complement component 5 Mice Inbred ICR Complement component 2 Insulin secretion Complement C5 Cell Biology Complement C3 Complement system Cell biology Receptors Complement 030104 developmental biology Endocrinology C5aR1 Glucose Alternative complement pathway Molecular Medicine Cytokines Original Article 030215 immunology |
| Zdroj: | Cellular and Molecular Life Sciences Atanes, P, Ruz Maldonado, I, Pingitore, A, Hawkes, R, Liu, B, Zhao, M, Huang, G C, Persaud, S J & Amisten, S 2017, ' C3aR and C5aR1 act as key regulators of human and mouse β-cell function ', Cellular and Molecular Life Sciences, pp. 1-12 . https://doi.org/10.1007/s00018-017-2655-1 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-017-2655-1 |
| Popis: | Aims Complement components 3 and 5 (C3 and C5) play essential roles in the complement system, generating C3a and C5a peptides that are best known as chemotactic and inflammatory factors. In this study we characterised islet expression of C3 and C5 complement components, and the impact of C3aR and C5aR1 activation on islet function and viability. Materials and methods Human and mouse islet mRNAs encoding key elements of the complement system were quantified by qPCR and distribution of C3 and C5 proteins was determined by immunohistochemistry. Activation of C3aR and C5aR1 was determined using DiscoverX beta-arrestin assays. Insulin secretion from human and mouse islets was measured by radioimmunoassay, and intracellular calcium ([Ca2+]i), ATP generation and apoptosis were assessed by standard techniques. Results C3 and C5 proteins and C3aR and C5aR1 were expressed by human and mouse islets, and C3 and C5 were mainly localised to β- and α-cells. Conditioned media from islets exposed for 1 h to 5.5 and 20 mM glucose stimulated C3aR and C5aR1-driven beta-arrestin recruitment. Activation of C3aR and C5aR1 potentiated glucose-induced insulin secretion from human and mouse islets, increased [Ca2+]i and ATP generation, and protected islets against apoptosis induced by a pro-apoptotic cytokine cocktail or palmitate. Conclusions Our observations demonstrate a functional link between activation of components of the innate immune system and improved β-cell function, suggesting that low-level chronic inflammation may improve glucose homeostasis through direct effects on β-cells. Electronic supplementary material The online version of this article (doi:10.1007/s00018-017-2655-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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