Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2004, PMID: 14557259

Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells.

Ouchi, Noriyuki; Kobayashi, Hideki; Kihara, Shinji; Kumada, Masahiro; Sato, Kaori; Inoue, Tatsuya; Funahashi, Tohru; Walsh, Kenneth

Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis (eNOS) in HUVECs. Transduction with either dominant-negative AMPK or dominant-negative Akt abolished adiponectin-induced eNOS phosphorylation as well as adiponectin-stimulated HUVEC migration and differentiation. Dominant-negative AMPK also inhibited adiponectin-induced Akt phosphorylation, suggesting that AMPK is upstream of Akt. Dominant-negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin-stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation. Finally, adiponectin stimulated blood vessel growth in vivo in mouse Matrigel plug implantation and rabbit corneal models of angiogenesis. These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.

Diseases/Pathways annotated by Medline MESH: Neovascularization, Pathologic
Document information provided by NCBI PubMed

Text Mining Data

Akt/protein → Adiponectin: " Adiponectin promoted the phosphorylation of AMP activated protein kinase (AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis ( eNOS ) in HUVECs "

AMP activated protein kinase (AMPK) → Adiponectin: " Adiponectin promoted the phosphorylation of AMP activated protein kinase (AMPK) , protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis ( eNOS ) in HUVECs "

Akt ⊣ AMPK: " Dominant negative AMPK also inhibited adiponectin induced Akt phosphorylation, suggesting that AMPK is upstream of Akt "

eNOS ⊣ Akt: " Dominant negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation "

Manually curated Databases

No curated data.