Figure 2.

Synergic interaction of Orz with organs-organelles. Endoplasmic reticulum (ER) stress results in misfolded protein accumulation and leads to pancreatic β-cell death by apoptosis. Orz decreases the expression of ER stress-responsive genes Ddit3, Dnajb9 and Xbp1s, and it consequently enhances β-cell insulin production. In addition, Orz improves the adipocyte production of adiponectin. Increased levels of insulin and adiponectin can activate 5′-AMP-activated protein kinase (AMPK) (via AdipoR1), which reduces the expression of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase, and inhibits gluconeogenesis. Furthermore, AMPK induces β-isoform of coenzyme A carboxylase (ACC-β) phosphorylation, which inhibits acetyl coenzyme A carboxylase (ACC) and results in increased fatty-acid oxidation. Full-length adiponectin activates peroxisome proliferator-activated receptors (PPAR-α) (via AdipoR2) and, thereby stimulating fatty-acid oxidation and decreasing triglyceride content in the tissues.