RNA-Seq Analysis of Islets to Characterise the Dedifferentiation in Type 2 Diabetes Model Mice db/db
| Autor: | Fang-Xu Jiang, Ramesh Ram, Abraham Neelankal John |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine endocrine system endocrine system diseases Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Biology Diabetes Mellitus Experimental Pathology and Forensic Medicine Islets of Langerhans Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Gene expression Animals Gene Transcription factor Insulin-like growth factor 1 receptor geography geography.geographical_feature_category Sequence Analysis RNA Gene Expression Profiling RNA General Medicine Cell Dedifferentiation Islet Cell biology 030104 developmental biology Diabetes Mellitus Type 2 biology.protein PDX1 GLUT2 Female Transcriptome |
| Zdroj: | Endocrine Pathology. 29:207-221 |
| ISSN: | 1559-0097 1046-3976 |
| DOI: | 10.1007/s12022-018-9523-x |
| Popis: | Type 2 diabetes (T2D) is a global health issue and dedifferentiation plays underlying causes in the pathophysiology of T2D; however, there is a lack of understanding in the mechanism. Dedifferentiation results from the loss of function of pancreatic β-cells alongside a reduction in essential transcription factors under various physiological stressors. Our study aimed to establish db/db as an animal model for dedifferentiation by using RNA sequencing to compare the gene expression profile in islets isolated from wild-type, db/+ and db/db mice, and qPCR was performed to validate those significant genes. A reduction in both insulin secretion and the expression of Ins1, Ins2, Glut2, Pdx1 and MafA was indicative of dedifferentiation in db/db islets. A comparison of the db/+ and the wild-type islets indicated a reduction in insulin secretion perhaps related to the decreased Mt1. A significant reduction in both Rn45s and Mir6236 was identified in db/+ compared to wild-type islets, which may be indicative of pre-diabetic state. A further significant reduction in RasGRF1, Igf1R and Htt was also identified in dedifferentiated db/db islets. Molecular characterisation of the db/db islets was performed via Ingenuity analysis which identified highly significant genes that may represent new molecular markers of dedifferentiation. |
| Databáze: | OpenAIRE |
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