FIG. 1.

Simplified schematic of insulin transduction pathways. PI-3 kinase pathway regulates NO production in the vascular endothelium and GLUT4 translocation in insulin-sensitive tissues, i.e., skeletal muscle. The mitogen-activated protein (MAP) kinase pathway regulates endothelin (ET-1) production in the vascular endothelium and downstream effects of growth and mitogenesis. The study by Wang et al. (19) implicates NO as a critical mediator of transendothelial insulin transport into the interstitial space, consequently promoting glucose uptake. NO purportedly increases insulin transport via protein S-nitrosylation (PTB1B). Potential role or cross talk with the MAP kinase pathway in mediating insulin transport remains open for investigation.