Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.

ABSTRACT: Chronic hyperglycemia, a defining feature of type 2 diabetes (T2D) and related metabolic disorders, exacerbates insulin resistance and impairs muscle glucose utilization, contributing to systemic metabolic dysfunction. While skeletal muscle is the primary site for postprandial glucose uptake and plays a pivotal role in maintaining whole-body glucose homeostasis, the molecular mechanisms by which hyperglycemia induces maladaptive responses in muscle remain poorly understood. Here, PAXIP1-associated glutamate-rich protein 1 (PAGR1) is identified as a glucose-responsive regulator in skeletal muscle, whose expression is induced by high glucose levels and modulates systemic glucose homeostasis and hepatic metabolism. Using muscle-specific PAGR1-knockout mice, it is demonstrated that PAGR1 defic

SUBMITTER: Ding C 

PROVIDER: S-EPMC12533408 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature