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PLoS One. 2018 Apr 27;13(4):e0196601. doi: 10.1371/journal.pone.0196601. eCollection 2018.

Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction.

Author information

1
Translational Science, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
2
Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
3
Translational Medicine Unit CVRM, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
4
Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
5
Offspring Biosciences, Södertälje, Sweden.
6
Bioscience, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Abstract

Beta cell dysfunction accompanies and drives the progression of type 2 diabetes mellitus (T2D), but there are few clinical biomarkers available to assess islet cell stress in humans. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on beta cell function in animals. However, its potential as a circulating biomarker released from human beta cells and islets has not been studied. In this study primary human islets, beta cells and plasma samples were used to explore secretion and expression of secretagogin in relation to the T2D pathology. Secretagogin was abundantly and specifically expressed and secreted from human islets. Furthermore, T2D patients had an elevated plasma level of secretagogin compared with matched healthy controls, which was confirmed in plasma of diabetic mice transplanted with human islets. Additionally, the plasma secretagogin level of the human cohort had an inverse correlation to clinical assessments of beta cell function. To explore the mechanism of secretagogin release in vitro, human beta cells (EndoC-βH1) were exposed to elevated glucose or cellular stress-inducing agents. Secretagogin was not released in parallel with glucose stimulated insulin release, but was markedly elevated in response to endoplasmic reticulum stressors and cytokines. These findings indicate that secretagogin is a potential novel biomarker, reflecting stress and islet cell dysfunction in T2D patients.

PMID:
29702679
PMCID:
PMC5922551
DOI:
10.1371/journal.pone.0196601
[Indexed for MEDLINE]
Free PMC Article

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