TRIM32 regulates insulin sensitivity by controlling insulin receptor degradation in the liver.

ABSTRACT: Impaired insulin receptor signaling is strongly linked to obesity-related metabolic conditions like non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes (T2DM). However, the exact mechanisms behind impaired insulin receptor (INSR) signaling in obesity induced by a high-fat diet remain elusive. In this study, we identify an E3 ubiquitin ligase, tripartite motif-containing protein 32 (TRIM32), as a key regulator of hepatic insulin signaling that targets the insulin receptor (INSR) for ubiquitination and proteasomal degradation in high-fat diet (HFD) mice. HFD induces the nuclear translocation of SREBP-1c (Sterol Regulatory Element-Binding Protein 1c), resulting in increased expression of TRIM32 in hepatocytes. TRIM32 ubiquitylates INSR and facilitates its proteasomal degradation, le

SUBMITTER: Thakur S 

PROVIDER: S-EPMC11811033 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature