Targeting of insulin receptor endocytosis as a treatment to insulin resistance.
Publication Title
Journal of diabetes and its complications
Document Type
Article
Publication Date
11-1-2023
Keywords
Humans; Receptor, Insulin; Insulin Resistance; Endocytosis; Clathrin; Insulin; Transcription Factors; Glucose; Homeodomain Proteins; DNA-Binding Proteins; Calcium-Binding Proteins; Trans-Activators; Clathrin-independent endocytosis; Clathrin-mediated endocytosis; Insulin receptor; Insulin resistance.; california; pni; santa monica
Abstract
BACKGROUND: Insulin resistance is the decreased effectiveness of insulin receptor function during signaling of glucose uptake. Insulin receptors are regulated by endocytosis, a process that removes receptors from the cell surface to be marked for degradation or for re-use.
OBJECTIVES: Our goal was to discover insulin-resistance-related genes that play key roles in endocytosis which could serve as potential biological targets to enhance insulin sensitivity.
METHODS: The gene mutations related to insulin resistance were elucidated from ClinVar. These were used as the seed set. Using the GeneFriends program, the genes associated with this set were elucidated and used as an enriched set for the next step. The enriched gene set network was visualized by Cytoscape. After that, using the VisANT program, the most significant cluster of genes was identified. With the help of the DAVID program, the most important KEGG pathway corresponding to the gene cluster and insulin resistance was found. Eleven genes part of the KEGG endocytosis pathway were identified. Finally, using the ChEA3 program, seven transcription factors managing these genes were defined.
RESULTS: Thirty-two genes of pathogenic significance in insulin resistance were elucidated, and then co-expression data for these genes were utilized. These genes were organized into clusters, one of which was singled out for its high node count of 58 genes and low p-value (p = 4.117 × 10
CONCLUSION: We believe that delaying removal of insulin receptors from the cell surface would prolong signaling of glucose uptake and counteract the symptoms of insulin resistance.
Clinical Institute
Neurosciences (Brain & Spine)
Clinical Institute
Kidney & Diabetes
Specialty/Research Institute
Endocrinology
Specialty/Research Institute
Neurosciences
DOI
10.1016/j.jdiacomp.2023.108615 http
