Plasma Secretagogin is Increased in Individuals with Glucose Dysregulation

Abstract

Objective Secretagogin, a Ca²⁺ binding protein, is one of the most abundant proteins in pancreatic β-cells and is critical for maintaining the structural integrity and signaling competence of β-cells. This study seeks to assess the concentrations of plasma secretagogin in participants with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (T2DM) and to explore its relationship to parameters of glucose and lipid metabolism, first-phase insulin secretion, insulin resistance and pancreatic β-cell function.

Materials and Methods A total of 126 eligible subjects were divided into three groups: a normal glucose tolerance (NGT, n=45), a pre-DM (n=30), and a T2DM (n=51) group. An intravenous glucose tolerance test (IVGTT) was performed, and clinical and biochemical parameters were measured for all subjects.

Results Plasma secretagogin levels were significantly higher in both pre-DM and T2DM patients compared with NGT subjects and were highest in the T2DM group. Correlation analysis showed that plasma secretagogin levels were positively correlated with fasting plasma glucose, postchallenge plasma glucose (2hPG), HbA1c and body mass index (BMI) but were not correlated with waist-hip ratio, blood pressure, lipid profiles, fasting serum insulin, homeostasis model assessment for insulin resistance, homeostasis model assessment for β-cell function and first-phase insulin secretion indicators. Multiple logistic regression analysis revealed that 2hPG and BMI were independent predictors for elevation of plasma secretagogin concentrations.

Conclusions Increased circulating secretagogin might be a molecular predictor for early diagnosis of diabetes. Further studies are needed to confirm this finding and explore the role of secretagogin in obesity.

Key words

secretagogin - diabetes - prediabetes - insulin secretion - obesity

Publication History

Received: 11 June 2019
Received: 08 August 2019

Accepted: 21 August 2019

Article published online:
23 September 2019

• References

• 1 Cho NH, Shaw JE, Karuranga S. et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138: 271-281
• 2 Petersen MC. Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev 2018; 98: 2133-2223
• 3 Wagner L, Oliyarnyk O, Gartner W. et al. Cloning and expression of secretagogin, a novel neuroendocrine- and pancreatic islet of Langerhans-specific Ca^2 + -binding protein.. J Biol Chem 2000; 275: 24740-24751
• 4 Uhlen M, Fagerberg L, Hallstrom BM. et al. Proteomics. Tissue-based map of the human proteome. Science 2015; 347: 1260419
• 5 Yang XY, Liu QR, Wu LM. et al. Overexpression of secretagogin promotes cell apoptosis and inhibits migration and invasion of human SW480 human colorectal cancer cells. Biomed Pharmacother 2018; 101: 342-347
• 6 Maj M, Gartner W, Ilhan A. et al. Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin. J Endocrinol 2010; 205: 25-36
• 7 Hansson SF, Zhou AX, Vachet P. et al. Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction.PLoS One 2018; 13: e0196601
• 8 Malenczyk K, Girach F, Szodorai E. et al. A TRPV1-to-secretagogin regulatory axis controls pancreatic β-cell survival by modulating protein turnover. EMBO J 2017; 36: 2107-2125
• 9 Yang SY, Lee JJ, Lee JH. et al. Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion.Biochem J 2016; 473: 1791-1803
• 10 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO: Consultation. Diabetic Medicine 1998; 15: 539-553
• 11 Liu Q, Lai M. Location and functions of secretagogin protein. Zhejiang Da Xue Xue Bao Yi Xue Ban 2016; 45: 56-60
• 12 Gartner W, Lang W, Leutmetzer F. et al. Cerebral expression and serum detectability of secretagogin, a recently cloned EF-hand Ca(2+)-binding protein. Cereb Cortex 2001; 11: 1161-1169
• 13 Bai Y, Sun Y, Peng J. et al. Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494. Oncotarget 2014; 5: 7760-7775
• 14 Khandelwal R, Sharma AK, Chadalawada S. et al. Secretagogin is a redox-responsive Ca²⁺ sensor. Biochemistry 2017; 56: 411-420
• 15 Lee JJ, Yang SY, Park J. et al. Calcium ion induced structural changes promote dimerization of secretagogin. Which is required for its insulin secretory function. Sci Rep 2017; 7: 6976
• 16 Kobayashi M, Yamato E, Tanabe K. et al. Functional analysis of novel candidate regulators of insulin secretion in the MIN6 mouse pancreatic β cell line. PLoS One 2016; 11: e0151927
• 17 Hasegawa K, Wakino S, Kimoto M. et al. The hydrolase DDAH2 enhances pancreatic insulin secretion by transcriptional regulation of secretagogin through a Sirt1-dependent mechanism in mice. FASEB J 2013; 27: 2301-2315
• 18 Bai Y, Sun Y, Peng J. et al Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494. Oncotarget 09/2014; 5: 7760-7775
• 19 Kim DS, Choi YP, Kang S. et al Panel of candidate biomarkers for renal cell carcinoma. J Proteome Res 2010; 9: 3710-3719
• 20 Montaner J, Mendioroz M, Ribó M. et al. A panel of biomarkers including caspase-3 and D-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department. J Intern Med 2011; 270: 166-174