Plasma Secretagogin is Increased in Individuals with Glucose Dysregulation.

OBJECTIVE: Secretagogin, a Ca2+ binding protein, is one of the most abundant proteins in pancreatic ß-cells and is critical for maintaining the structural integrity and signaling competence of ß-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 ß-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 ß-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.

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

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-ßH1) 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.

Secretagogin (SCGN) Plasma Levels and their Association with Cognitive and Social Behavior in Children with Autism Spectrum Disorder ASD).

OBJECTIVE: To investigate the secretagogin (SCGN) plasma levels in children with autism spectrum disorder (ASD) compared to age and gender-matched healthy control, and its association with cognitive and social behaviors by using childhood autism rating scale (CARS) and social responsiveness scale (SRS). STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2015 to May 2016. METHODOLOGY: SCGN levels were determined in the plasma of thirty-seven (37) autistic children using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their CARS scores and compared with thirty (30) age and gender-matched control samples. Correlation between SCGN levels and different cognitive and social behavior scales (CARS and SRS) was determined by Spearman's correlation coefficient (r). RESULTS: The results indicated that autistic children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7 (26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5 (27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p = 0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. However, there was no significant difference between the SCGN levels of children with mild to moderate and severe autism (p = 0.66). Spearman's correlation coefficient (r) was used to determine the relationships between SCGN levels and different variables (CARS, SRS). However, the results showed no significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86; SRS, r=0.21, p=0.20). CONCLUSION: The low SCGN plasma levels in children with ASD probably indicate that SCGN might be implicated in the pathogenesis of autism. However, these data should be treated with caution until further investigations are performed using larger sample sizes to determine whether the decrease in plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role in the disease.