Figure 1:

Insulin-sensitizing effects of adiponectin. Upon release from adipocytes, adiponectin circulates and targets three metabolic tissue/organs liver, muscle and adipose tissue, by binding to its own receptors AdipoR1 and AdipoR2, adiponectin activates AMPK and PPARα and subsequently sensitizes insulin signaling, promoting glucose update and inhibiting glucose production in liver and muscle respectively, in addition to enhanced fatty acid oxidation in both tissues. Adiponectin via APPL1 facilitates the binding of IRS1/2 to insulin receptor through which enhances insulin receptor downstream signaling. In addition, adiponectin stimulates the activation of ceramidase and reduces intracellular and circulating levels of ceramide, improving insulin resistance. IR, insulin receptor; IRS, insulin receptor substrate; PI3K, phosphoinositide 3-kinase; FoxO1, Forkhead Box O1; PEPCK, phosphoenolpyruvate carboxykinase; G6Pase, glucose-6-phosphatase; IL-6, interleukin-6; NF-κB, nuclear factor-κB; STAT3, signal transducer and activator of transcription 3; LKB1, liver kinase B1; AMPK, AMP-activated protein kinase; PPAR-α, peroxisome proliferator-activated receptor-α; SREBP1c, sterol regulatory element-binding protein 1c; ACC, acetyl coenzyme A carboxylase; S1P, sphingosine-1-phosphate; FFA/TG, free fatty acid/triglycerides; APPL1, adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1; CaMBBβ, Calcium/calmodulin-dependent protein kinase kinase β; SIRT1, sirtuin 1; PGC-1α, Peroxisome proliferator-activated receptor-gamma coactivator-1α; ER, endoplasmic reticulum; JNK, c-Jun N-terminal kinase.