Regulation of insulin signaling via myosin motor protein and actin cytoskeletal network

Impairment of systemic insulin action causes insufficient glucose uptake to cells and compensatory hyper-secretion of insulin from pancreatic β-cells. This insulin-resistant state promotes development of type 2 diabetes, obesity, hypertension, dyslipidemia, and atherosclerosis. Numerous attempts have been made to clarigy this pathogenesis and molocular mechanisms of insulin resistance. Tumor necrosis factor-α(TNF-α) is one of adipocytokines and a major factor causing insulin resistance. This cytokine attenuates insulin signaling by phosphorylation of insulin receptor substrate-1(IRS-1) Ser residues. However little is known about the precise molecular mechanisms. Recently we reported that IκB kinase-β(IKK-β) interacted with IRS-1, and phosphorylated IRS-1 Ser^<307> through molecular motor and actincytoskeleton. In this review, we overview this unique molecular mechanism and propose a new model that molecular motor and cytoskeletal network organize signaling cross-talk.

NEMO

IKK-γ

Myo1c

IRS-1

TNF-α

insulin resistance