Insulin resistance is a major risk for development of type 2 diabetes. Several genes involved in regulation of insulin receptor substrate 1 (IRS1) and lead to chronic diabetes. Our RNA sequence data from kidney of diabetic mice show a new candidate gene involved in the regulation of IRS1. New candidate gene, Tripartite motif protein 29 (TRIM29), acts as an E3 ligase targeting insulin receptor (IR) and insulin receptor substrate 1 (IRS1) for ubiquitin-dependent degradation, resulting in insulin resistance. RNA seq data show that TRIM29 is higher 2.5 and 3.6 fold in kidney cortex of diabetic mice (db/db) at age of 10 and 12 months compared to wild type mice, respectively. Mouse renal proximal tubular epithelial cells treated with high glucose (25mM) for 48 hours showed significant increased in TRIM29 and decreased in IRS-1 compared to cells grown in normal glucose (5mM). Pre-transfected cells with siRNA against TRIM29 resulted in significant increased IRS-1 and cell proliferative marker, cyclin D1 expression. Downregulation of tuberin by siRNA significantly decreased TRIM29 expression and increased cyclin D1 expression. In addition, downregulation of AMPK by DN-AMPK and compound C resulted in significant decreased TRIM29 compared to cells transfected with control-siRNA. Kidney cortex of db/db mice and WT mice at age 10 and 12 months were analyzed by Western blot showed that TRIM29 is significantly increased and IRS-1 decreased compared to wild type mice. Increase TRIM29 in kidney diabetic mice was associated with increased in cyclin D1. Here, we identified a new candidate gene, TRIM29 that involves in the regulation IRS-1 pathways to increase cell proliferation and enhance insulin resistance diabetes. The new gene, TRIM29, may be used as a new candidate target to treat insulin resistant in diabetes.
S.L. Habib: None.