Voelcker Academy

Research Symposium 2011

 

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Marisela Casanova

Molecular Mechanism of Adiponectin Signaling

Marisela Casanova

Mentor(s): Lily Q. Dong Ph.D.

Type 2 diabetes is a chronic disease that affects the way the body metabolizes glucose and is associated with increased prevalence of Western diet, lack of exercise, and the increase in obesity in the human population. This occurs when there is a loss of insulin sensitivity in the insulin target tissues, such as liver, adipose tissue, and skeletal muscle, causing an interference in glucose metabolism through impaired insulin signaling. An adipose tissue secreted hormone, adiponectin, is positively correlated with insulin sensitivity, suggesting a direct cross between adiponectin and insulin pathways in that they both regulate energy homeostasis, however the molecular mechanism of the adiponectin signaling pathways is not fully known. An adaptor protein, APPL1, is the first protein to be identified in the adiponectin signaling pathway that interacts directly with the adiponectin receptors, AdipoR1 and AdipoR2. Adiponectin stimulates the interaction of APPL1 to the intracellular portion of AdipoR1/2 in many mammalian cells and stimulates adiponectin signaling inducing the activation of multiple cellular signaling pathways that drive glucose metabolism, lipid oxidation, and the translocation of GLUT4 transporters to the cellular membrane. In addition to APPL1, our laboratory has identified the APPL1 isoform APPL2 as another signaling molecule regulating adiponectin signaling. APPL1 and APPL2 have similar domain structures but are coded by different genes. In contrast to APPL1, APPL2 inhibits adiponectin signaling by binding to the adiponectin receptors to block the signal. These findings indicate that APPL1/2 function as an integrated Yin-Yang regulator of adiponectin signaling, which coordinately regulates glucose and lipid metabolism. Better understanding the adiponectin mechanism could potentially serve as a therapeutic drug in treating type 2 diabetes and obesity.