Hyperglycemia Increased the Expression of Calcrl G Protein-Coupled Receptor in Monocytes From Diabetic Patients Publisher



Azarshin SZ ; Marashi M ; Kichi ZA ; Boroumand M ; Behmanesh M
Source: Cell Journal Published:2025

Abstract

Objective: Diabetes is a metabolic disorder with two common categories of complications: microvascular and macrovascular. Cardiovascular diseases (CVDs), which are linked to inflammation in the blood vessels, are the most important complications of diabetes. G protein-coupled receptors (GPCRs) play a crucial role in initiating these inflammatory responses. The aim of this study is to identify GPCRs that may respond to high blood glucose in monocyte cells and have an effect on regulating vascular inflammation. Materials and Methods: In this in-silico and experimental study, first, RNA sequencing (RNAseq) data from monocytes from the blood of diabetic patients were analyzed to find the GPCR most responsive to high blood sugar. Next, the expression correlation of the candidate GPCR with inflammatory genes was calculated, and expression changes in THP-1 cells under hyperglycemia were evaluated via quantitative polymerase chain reaction (qPCR). Finally, the effect of the candidate GPCR on down-regulation of NF-kB mRNA expression, generation of reactive oxygen species (ROS), and caspase activity was evaluated. Results: The RNAseq analysis showed that expression of Calcitonin receptor-like (CALCRL), one of the GPCR candidates, increased in the monocytes of patients with diabetes compared to healthy individuals. The qPCR result also indicated that expression of the CALCRL gene increased in THP-1 cells treated with 25 mM D-glucose. Correlation analyses demonstrated that increased expression of CALCRL is associated with inflammatory pathways, cytokine production and secretion, and the cell migration process. Finally, our data indicated that CALCRL downregulation decreased inflammation related to hyperglycemia, including NF-kB mRNA expression, ROS production, and caspase 3/7 activity. Conclusion: Hyperglycemia increased the expression of CALCRL GPCR in the monocytes of diabetic patients. The CALCRL receptor may play a key role in regulating vascular inflammation in hyperglycemic conditions. Targeting CALCRL may control inflammation in blood cells. © 2025, Royan Institute (ACECR). All rights reserved.