The project aims to investigate the role of proinsulin C-peptide and G-protein coupled receptor 146 (GPR146) in type 2 diabetes mellitus (T2DM) complications. C-peptide is a short peptide that influences multiple cellular pathways, and its role in diabetes complications has become increasingly evident. The study postulates that C-peptide interacts with the GPR146 receptor, which may be involved in cholesterol metabolism, potentially explaining the association of C-peptide with atherosclerosis in type 2 diabetes.

The study’s objective is to examine the network of genes regulated by GPR146 and the expression patterns of GPR146 in tissues affected by diabetes-related complications in patients undergoing cardiovascular surgery. The research will focus on patients with type 2 diabetes and individuals without diabetes who require cardiac surgical procedures. Tissue sampling during these procedures will allow the investigation of the interaction between C-peptide and the potential receptor in the tissues of individuals affected by type 2 diabetes.

The study will involve the analysis of cellular pathways regulated by C-peptide-GPR146 signaling using techniques suitable for large-scale gene expression studies. Additionally, the study will assess the associations between C-peptide levels and the concentrations of zinc, albumin, cholesterol, LDL, triglycerides, and GPR146 expression in the human body.

The main goal of the study is to elucidate whether and which processes related to type 2 diabetes complications are linked to signaling through GPR146. The findings from this research could form the basis for potential pharmacological interventions utilizing C-peptide and identifying relevant endpoints associated with this overlooked hormone, which may be significant in the prevention or treatment of type 2 diabetes complications.

The project is funded by the National Science Centre (NCN) under the Preludium 21 grant, no. 2022/45/N/NZ4/01206. For more information, please refer to the provided link.