MicroRNA-17-92 cluster regulates pancreatic beta-cell proliferation and adaptation
| Autor: | Xiang Chen, Kun Zhang, Li Tian, Shan Wan, Ying Xie, Chunyu Wang, Haoming Tian, Qian Zhao, Xiao Ji, Yaxi Chen, Xijie Yu, Janet M. Hock |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Phosphatase Apoptosis Biology medicine.disease_cause Diet High-Fat Biochemistry Cell Line 03 medical and health sciences Endocrinology Pancreatic beta cell proliferation Internal medicine Insulin-Secreting Cells microRNA Glucose Intolerance Insulin Secretion medicine Tensin PTEN Animals Insulin Molecular Biology Cell Proliferation Mice Knockout geography geography.geographical_feature_category Islet Adaptation Physiological Mice Inbred C57BL MicroRNAs 030104 developmental biology Glucose Phenotype Gene Expression Regulation biology.protein Adaptation Carcinogenesis Gene Deletion Signal Transduction |
| Zdroj: | Molecular and cellular endocrinology. 437 |
| ISSN: | 1872-8057 |
| Popis: | MiR-17-92 cluster contributes to the regulation of mammalian development, aging and tumorigenesis. The functional roles of miR-17-92 in pancreatic beta-cells are largely unknown. In this study, we found that conditional deletion of miR-17-92 in mouse pancreatic beta-cells (miR-17-92βKO) significantly reduces glucose tolerance and the first phase of insulin secretion, despite normal ad libitum fed and fasting glucose levels. Proliferation is down-regulated in pancreatic beta-cells after deleting miR-17-92. MiR-17-92βKO mice show higher phosphatase and tensin homologue (PTEN) and lower phosphorylated AKT in islets. Under high fat diet challenge for 16 weeks, miR-17-92βKO mice lose compensation and exhibit higher glucose levels, and lower insulin secretion. Collectively, these data suggest that miR-17-92 is a critical contributor to molecular mechanisms regulating glucose-stimulated insulin secretion and pancreatic beta-cell adaptation under metabolic stress. |
| Databáze: | OpenAIRE |
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