Ornithine decarboxylase 1 and solute carrier transporters: Coordinated gene expression in response to glucotoxicity, an in vitro investigation

Abstract

Solute carrier (SLC) transporters have been linked to type 2 diabetes (T2D) and play a crucial role in cellular metabolism. Growth and metabolism depend on ornithine decarboxylase 1 (ODC1), a crucial regulator of polyamine production, especially in the pancreas. This study examines the interaction between ODC1 and SLC gene expressions under glucotoxicity conditions, which simulate hyperglycemia. In silico analysis of human pancreatic β-islet tissue datasets from T2D patients identified differentially expressed SLC genes. In vitro studies were conducted using HEK293T cells and COS-7 cell lines. Overexpression and knockdown of ODC1 in HEK293T cells revealed ODC1's influence on the mRNA expression profiles of SLC. In vitro overexpression with and without high glucose also revealed ODC1's influence on SLC genes. Specifically, ODC1 modulated the expression of SLC11A2, SLC30A1, SLC39A6, and other SLCs, including SLC17A6, SLC25A12, SLC26A2, SLC35A5, SLC38A2, SLC9A6, SLC6A8, and SLC20A1. Glucotoxicity mostly suppressed SLC gene expression; however, ODC1 overexpression partially reversed this effect for certain SLCs. This work highlights an unrecognized regulatory network involving ODC1 and SLCs, suggesting a potential role for polyamine pathway modulation in controlling transport dynamics. These findings suggest a novel regulatory network where ODC1 influences SLC gene expression, impacting metabolic pathways and nutrient transport. This study provides preliminary evidence that ODC1 may be a potential regulator of SLC transporters, offering new insights into the metabolic dysregulation of T2D and potential therapeutic targets.