AUTHOR=Songtao Yang , Fangyu Li , Jie Cao , Li Yuan 

TITLE=Identification of claudin-2 as a promising biomarker for early diagnosis of pre-diabetes

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1370708

DOI=10.3389/fphar.2024.1370708

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Pre-diabetes, a high-risk metabolic state, is situated between normal glucose homeostasis and diabetes. Early identification of pre-diabetes offers opportunities for intervention and diabetes reversal, highlighting the crucial need to investigate reliable biomarkers for this condition.</p><p><bold>Methods:</bold> We conducted an in-depth bioinformatics analysis of clinical samples from non-diabetic (ND), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) categories within the GSE164416 dataset. Thereafter the HFD and STZ treated mice were used for validation.</p><p><bold>Results:</bold> This analysis identified several codifferentially expressed genes (Co-DEGs) for IGT and T2DM, including <italic>CFB</italic>, <italic>TSHR</italic>, <italic>VNN2</italic>, <italic>APOC1</italic>, <italic>CLDN2</italic>, <italic>SLPI</italic>, <italic>LCN2</italic>, <italic>CXCL17</italic>, <italic>FAIM2</italic>, and <italic>REG3A</italic>. Validation of these genes and the determination of ROC curves were performed using the GSE76895 dataset. Thereafter, <italic>CLDN2</italic> was selected for further verification. Gene expression analysis and immunofluorescence analysis revealed a significant upregulation of <italic>CLDN2</italic> expression in the pancreas islets of mice in the high-fat diet and T2DM groups compared to the control group. Similarly, serum level of <italic>CLDN2</italic> in patients with IGT and T2DM were significantly higher than those in the healthy group.</p><p><bold>Discussion:</bold> These results suggest that <italic>CLDN2</italic> can serve as a novel biomarker for pre-diabetes, providing a new direction for future research in the prevention of type 2 diabetes.</p>