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

Protein Eng. Des. Sel.2019 Dec 13;32(2):67-76
Meghan F Hogan 1 , Mark Ziemann 2 , Harikrishnan K N 2 , Hanah Rodriguez 2 , Antony Kaspi 2 , Nathalie Esser 1 , Andrew T Templin 1 , Assam El-Osta 3 , Steven E Kahn 1
Meghan F Hogan 1 , Mark Ziemann 2 , Harikrishnan K N 2 , Hanah Rodriguez 2 , Antony Kaspi 2 , Nathalie Esser 1 , Andrew T Templin 1 , Assam El-Osta 3 , Steven E Kahn 1
+ et al

[No authors listed]

Author information
  • 1 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA 98018, USA.
  • 2 Epigenetics in Human Health and Disease, Department of Diabetes, Monash University, Melbourne, VIC 3004, Australia.
  • 3 University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science, Copenhagen, Denmark.

摘要


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.

KEYWORDS: RNA-seq, amylin, amyloid, diabetes, glucose, islet amyloid polypeptide, islets, steroidogenic acute regulatory protein, β-cell