1984-LB: Secretagogin—A Potential Circulating Biomarker of Acute Pancreatic ß-Cell Injury

Introduction & Objective: Beta cell dysfunction is the fundamental pathogenesis of type 1 diabetes mellitus (T1DM), but there are few clinical biomarkers available to assess β-cell injury. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on β-cell function in animals. However, its potential as a circulating biomarker released from injured islet β-cell has not been studied.

Methods: Streptozotocin (STZ) induced diabetes mouse model and 21 T1DM patient were recruited to explore secretion and expression of secretagogin in relation to the T1DM pathology. Secretagogin expression was detected by western blotting and immunofluorescence staining while circulating secretagogin levels was measured by ELISA kit.

Results: Secretagogin was abundantly expressed in mouse and human islets, specifically co-localized with insulin positive β-cell. STZ administration induced loss of β-cell and progressive depletion of pancreatic secretagogin. There’s a sharp peak in mouse plasma secretagogin level 24 h after STZ injection and declined gradually. Western blot analysis also revealed a notable reduction in secretagogin levels within the pancreas 1 week following the STZ treatment. Furthermore, T1DM patients exhibited a significant decrease in plasma secretagogin levels compared to matched healthy controls. Interestingly, 4 subjects with fulminant type 1 diabetes (FT1DM) displayed considerably higher plasma secretagogin concentrations during the early stage of disease onset, in comparison to the average levels observed within the cohort. However, a clinical follow-up study revealed a significant reduction in plasma secretagogin levels among all FT1DM subjects during the observation period.

Conclusion: Our findings indicate that secretagogin is a potential novel biomarker reflecting acute pancreatic β-cell injury.