Abstract
Type 2 diabetes mellitus (T2DM) has insulin resistance (IR) or reduced β-cell mass, partially due to an increased β-cell apoptosis rate. Pancreatic stone protein/regenerating protein (PSP/reg) is a secretory protein produced in the pancreas and up-regulated dramatically during pancreatic disease. Recent studies revealed that β-cells undergoing apoptosis induce PSP/reg expression in surviving neighboring cells. Further experiments demonstrated that PSP/reg was elevated during disease progression in type 1 diabetes mellitus (T1DM). However, the association between PSP/reg and T2DM patients is unknown. The aim of this pilot study was to investigate PSP/reg in different clinical stages of T2DM and evaluate its correlation with chronic complications of diabetes. A total of 1,121 participants (479 males, 642 females; age range 23–80 years) were enrolled in this study. PSP/reg serum values were measured by a newly developed enzyme-linked immunosorbent assay (ELISA). We analyzed its correlation with clinical and biochemical parameters in subjects with T2DM at different clinical phases. Statistical analyses were conducted using SPSS 17.0 software. Correlations of PSP/reg and clinical parameters were performed using Spearman’s rank correlation coefficient. Differences between groups were determined by Nemenyi test. PSP/reg was elevated in high-risk and impaired glucose regulation (IGR) patients (p < 0.05). PSP/reg was significantly up-regulated in newly diagnosed T2DM patients and long-term diabetes patients with complications (p < 0.001). PSP/reg levels correlated with the duration of diabetes (p < 0.001). The area under the curve (AUC) for presence of diabetes-onset and its chronic complications was 0.640 and 0.754, respectively. PSP/reg is significantly up-regulated in T2DM patients, and PSP/reg levels are related to the duration of diabetes. Therefore, PSP/reg might be useful as a predictor of T2DM and disease progression.
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Acknowledgments
We would like to thank Martha Bain for excellent technical support. The project was supported in part by the Chinese Natural Science Foundation No.81270010, 30900696, 81170716 and the Gebert Rüf Foundation, GRS014/12 (Switzerland).
Conflict of interest
Rolf Graf is inventor of PSP in sepsis (Method for assaying sepsis in humans) for which the University of Zurich holds a patent.
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Jiayue Yang and Ling Li have contributed equally to this article. Zilin Sun and Rolf Graf contributed equally and are co-corresponding authors.
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Yang, J., Li, L., Raptis, D. et al. Pancreatic stone protein/regenerating protein (PSP/reg): a novel secreted protein up-regulated in type 2 diabetes mellitus. Endocrine 48, 856–862 (2015). https://doi.org/10.1007/s12020-014-0427-3
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DOI: https://doi.org/10.1007/s12020-014-0427-3