Islet Pericytes Are Required for β-Cell Maturity
| Autor: | Alona Epshtein, Lina Sakhneny, Daria Baer, Adi Sasson, Limor Landsman, Eleonor Rachi, Michal Lisnyansky |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse endocrine system medicine.medical_specialty Maf Transcription Factors Large Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Fluorescent Antibody Technique Biology Mice 03 medical and health sciences Insulin-Secreting Cells Internal medicine Gene expression Internal Medicine medicine Animals Homeostasis Pancreas Transcription factor Homeodomain Proteins geography geography.geographical_feature_category Insulin Cell Differentiation Flow Cytometry Islet 030104 developmental biology medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 Trans-Activators PDX1 Pericytes Transcription Factors |
| Zdroj: | Diabetes. 65:3008-3014 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db16-0365 |
| Popis: | β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin–based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with β-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to β-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood flow–independent role in maintaining β-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for β-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to β-cell dysfunction and disease progression. |
| Databáze: | OpenAIRE |
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