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RNA-seq-based identification of Star upregulation by islet amyloid formation

Version 2 2024-06-04, 15:43
Version 1 2019-10-23, 12:52
journal contribution
posted on 2024-06-04, 15:43 authored by MF Hogan, Mark ZiemannMark Ziemann, H K N, H Rodriguez, A Kaspi, N Esser, AT Templin, A El-Osta, SE Kahn
AbstractAggregation of islet amyloid polypeptide (IAPP) into islet amyloid results in β-cell toxicity in human type 2 diabetes. To determine the effect of islet amyloid formation on gene expression, we performed ribonucleic acid (RNA) sequencing (RNA-seq) analysis using cultured islets from either wild-type mice (mIAPP), which are not amyloid prone, or mice that express human IAPP (hIAPP), which develop amyloid. Comparing mIAPP and hIAPP islets, 5025 genes were differentially regulated (2439 upregulated and 2586 downregulated). When considering gene sets (reactomes), 248 and 52 pathways were up- and downregulated, respectively. Of the top 100 genes upregulated under two conditions of amyloid formation, seven were common. Of these seven genes, only steroidogenic acute regulatory protein (Star) demonstrated no effect of glucose per se to modify its expression. We confirmed this differential gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and also demonstrated the presence of STAR protein in islets containing amyloid. Furthermore, Star is a part of reactomes representing metabolism, metabolism of lipids, metabolism of steroid hormones, metabolism of steroids and pregnenolone biosynthesis. Thus, examining gene expression that is differentially regulated by islet amyloid has the ability to identify new molecules involved in islet physiology and pathology applicable to type 2 diabetes.

History

Journal

Protein Engineering, Design and Selection

Volume

32

Pagination

67-76

Location

England

Open access

  • Yes

ISSN

1741-0126

eISSN

1741-0134

Language

English

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2019, The Author(s)

Issue

2

Publisher

OXFORD UNIV PRESS