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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers / blood
  • Cell Nucleus / metabolism
  • Cohort Studies
  • Cytokines / metabolism
  • Cytoplasm / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Endoplasmic Reticulum / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucagon / metabolism
  • Glucose / pharmacology
  • Glucose Tolerance Test
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiopathology
  • Islets of Langerhans Transplantation
  • Male
  • Mice
  • Middle Aged
  • Secretagogins / blood*


  • Biomarkers
  • Cytokines
  • SCGN protein, human
  • Secretagogins
  • Glucagon
  • Glucose

Grant support

The clinical studies were supported by grants from AstraZeneca R&D, EXODIAB (Excellence of Diabetes Research in Sweden), the Swedish Diabetes Foundation and ALF grants. JWE has research grant or consultancy for AstraZeneca, Bristol-Myers-Squibb, Merck Sharpe & Dohme and NovoNordisk. Authors with affiliation AstraZeneca are employed by AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We confirm that the funder AstraZeneca provided support in the form of salaries for authors [SFH, AZ, SS, MCM, DK, AA, MSW, PD], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section.