RNA-sequencing of WFS1-deficient pancreatic islets.



Ivask, Marilin ORCID: 0000-0002-3512-5052, Hugill, Alison and Kõks, Sulev ORCID: 0000-0001-6087-6643
(2016) RNA-sequencing of WFS1-deficient pancreatic islets. Physiological reports, 4 (7). e12750 - ?.

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Abstract

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in theWFS1gene.WFS1encodes an endoplasmic reticulum resident transmembrane protein. TheWfs1-null mice exhibit progressive insulin deficiency and diabetes. The aim of this study was to describe the insulin secretion and transcriptome of pancreatic islets inWFS1-deficient mice.WFS1-deficient (Wfs1KO) mice had considerably less pancreatic islets than heterozygous (Wfs1HZ) or wild-type (WT) mice. Wfs1KOpancreatic islets secreted less insulin after incubation in 2 and 10 mmol/L glucose and with tolbutamide solution compared toWTand Wfs1HZislets, but not after stimulation with 20 mmol/L glucose. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KOhad an increased level of proinsulin. After incubation in 2 mmol/L glucose solution the proinsulin/insulin ratio in Wfs1KOwas significantly higher than that ofWTand Wfs1HZRNA-seq from pancreatic islets found melastatin-related transient receptor potential subfamily member 5 protein gene (Trpm5) to be downregulated inWFS1-deficient mice. Functional annotation ofRNAsequencing results showed thatWFS1 deficiency influenced significantly the pathways related to tissue morphology, endocrine system development and function, molecular transport network.

Item Type: Article
Uncontrolled Keywords: Islets of Langerhans, Animals, Mice, Inbred C57BL, Mice, Knockout, Wolfram Syndrome, Genetic Predisposition to Disease, Tolbutamide, Insulin, Proinsulin, Glucose, Membrane Proteins, RNA, Hypoglycemic Agents, Tissue Culture Techniques, Gene Expression Profiling, Sequence Analysis, RNA, Transcription, Genetic, Gene Expression Regulation, Heterozygote, Phenotype, Databases, Genetic, TRPM Cation Channels, Gene Regulatory Networks, Mice, 129 Strain, Real-Time Polymerase Chain Reaction, Transcriptome, Insulin Secretion
Depositing User: Symplectic Admin
Date Deposited: 17 Jul 2017 08:55
Last Modified: 20 Aug 2022 05:12
DOI: 10.14814/phy2.12750
URI: https://livrepository.liverpool.ac.uk/id/eprint/3008498