Toward Ameliorating Insulin Resistance: Targeting a Novel PAK1 Signaling Pathway Required for Skeletal Muscle Mitochondrial Function.

ABSTRACT: The p21-activated kinase 1 (PAK1) is required for insulin-stimulated glucose uptake in skeletal muscle cells. However, whether PAK1 regulates skeletal muscle mitochondrial function, which is a central determinant of insulin sensitivity, is unknown. Here, the effect of modulating PAK1 levels (knockdown via siRNA, overexpression via adenoviral transduction, and/or inhibition of activation via IPA3) on mitochondrial function was assessed in normal and/or insulin-resistant rat L6.GLUT4myc and human muscle (LHCN-M2) myotubes. Human type 2 diabetes (T2D) and non-diabetic (ND) skeletal muscle samples were also used for validation of the identified signaling elements. PAK1 depletion in myotubes decreased mitochondrial copy number, respiration, altered mitochondrial structure,

SUBMITTER: Balakrishnan R 

PROVIDER: S-EPMC10525748 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature