Pancreatic stone protein/regenerating protein is a potential biomarker for endoplasmic reticulum stress in beta cells

Endoplasmic reticulum (ER) stress in beta cells is an important pathogenic component of both type 1 and type 2 diabetes mellitus, as well as genetic forms of diabetes, especially Wolfram syndrome. However, there are currently no convenient ways to assess ER stress in beta cells, raising the need for...

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Bibliographic Details
Published in:Scientific reports 2019-03, Vol.9 (1), p.5199, Article 5199
Main Authors: Stone, Stephen, Abreu, Damien, Mahadevan, Jana, Asada, Rie, Kries, Kelly, Graf, Rolf, Marshall, Bess A., Hershey, Tamara, Urano, Fumihiko
Format: Article
Language:English
Subjects:
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Adult
Animal models
Animals
Beta cells
Biomarkers
Biomarkers - blood
Cell culture
Child
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetes mellitus (non-insulin dependent)
Endoplasmic reticulum
Endoplasmic Reticulum Stress
Humanities and Social Sciences
Humans
Insulin-Secreting Cells - metabolism
Lithostathine - blood
Lithostathine - metabolism
Male
Membrane Proteins - metabolism
Mice, Knockout
Models, Biological
multidisciplinary
Pancreas
Proteins
Rats
Science
Science (multidisciplinary)
Thapsigargin
Tunicamycin
Wolfram Syndrome - blood
Young Adult
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Summary:Endoplasmic reticulum (ER) stress in beta cells is an important pathogenic component of both type 1 and type 2 diabetes mellitus, as well as genetic forms of diabetes, especially Wolfram syndrome. However, there are currently no convenient ways to assess ER stress in beta cells, raising the need for circulating ER stress markers indicative of beta cell health. Here we show that pancreatic stone protein/regenerating protein (PSP/reg) is a potential biomarker for ER stressed beta cells. PSP/reg levels are elevated in cell culture and mouse models of Wolfram syndrome, a prototype of ER stress-induced diabetes. Moreover, PSP/reg expression is induced by the canonical chemical inducers of ER stress, tunicamycin and thapsigargin. Circulating PSP/reg levels are also increased in some patients with Wolfram syndrome. Our results therefore reveal PSP/reg as a potential biomarker for beta cells under chronic ER stress, as is the case in Wolfram syndrome.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-41604-4