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

Hogan, Meghan F., Ziemann, Mark, K N, Harikrishnan, Rodriguez, Hanah, Kaspi, Antony, Esser, Nathalie, Templin, Andrew T., El-Osta, Assam and Kahn, Steven E. 2019, RNA-seq-based identification of Star upregulation by islet amyloid formation, Protein engineering, design and selection, vol. 32, no. 2, pp. 67-76, doi: 10.1093/protein/gzz022.

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Title RNA-seq-based identification of Star upregulation by islet amyloid formation
Formatted title RNA-seq-based identification of Star upregulation by islet amyloid formation
Author(s) Hogan, Meghan F.
Ziemann, MarkORCID iD for Ziemann, Mark orcid.org/0000-0002-7688-6974
K N, Harikrishnan
Rodriguez, Hanah
Kaspi, Antony
Esser, Nathalie
Templin, Andrew T.
El-Osta, Assam
Kahn, Steven E.
Journal name Protein engineering, design and selection
Volume number 32
Issue number 2
Start page 67
End page 76
Total pages 10
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2019-02
ISSN 1741-0126
1741-0134
Summary Aggregation 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.
Language eng
DOI 10.1093/protein/gzz022
Indigenous content off
Field of Research 03 Chemical Sciences
06 Biological Sciences
10 Technology
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2019, The Author(s)
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30130836

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.