RNA-Seq Analysis of Islets to Characterise the Dedifferentiation in Type 2 Diabetes Model Mice db/db

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 transcr...

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Bibliographic Details
Published in:Endocrine pathology 2018-09, Vol.29 (3), p.207-221
Main Authors: Neelankal John, Abraham, Ram, Ramesh, Jiang, Fang-Xu
Format: Article
Language:English
Subjects:
Animals
Cell Dedifferentiation - genetics
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 2 - genetics
Endocrinology
Female
Gene expression
Gene Expression Profiling
Glucose transporter
Insulin
Insulin secretion
Islets of Langerhans
Male
Medicine
Medicine & Public Health
Mice
Oncology
Pancreas
Pathology
Ribonucleic acid
RNA
Rodents
Secretion
Sequence Analysis, RNA
Transcription factors
Transcriptome
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Summary: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.
ISSN:1046-3976
1559-0097
DOI:10.1007/s12022-018-9523-x