Dual leucine zipper-bearing kinase DLK is necessary for cell autonomous regulation of insulin sensitivity.

ABSTRACT: Metabolic syndrome and insulin resistance are driven in part by dysregulated signaling through the c-Jun N-terminal kinase (JNK) pathway. The scaffold protein JIP1 and its upstream kinase DLK (dual leucine zipper kinase) form a dynamic signaling complex that modulates JNK activity, yet the physiological role of DLK in glucose metabolism remains undefined. Here, we identify DLK as a critical regulator of insulin sensitivity using three genetically modified mouse models: a hypomorphic DLK allele, a tamoxifen-inducible whole-body DLK knockout, and a high-fat diet-induced obese model with DLK ablation. All models exhibited enhanced insulin sensitivity independent of adiposity, characterized by increased glucose uptake in muscle and adipose tissue, and improved suppression of hepatic glucose pr

SUBMITTER: Wong HN 

PROVIDER: S-EPMC12544161 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature