RNA-sequencing of WFS1-deficient pancreatic islets

Ivask, Marilin, Hugill, Alison and Koks, 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:	Insulin, RNA-sequencing, Trpm5, Wfs1
Depositing User:	Symplectic Admin
Date Deposited:	17 Jul 2017 08:55
Last Modified:	19 Jan 2023 06:59
DOI:	10.14814/phy2.12750
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008498