Adiponectin is a hormone secreted by fat cells, involved in the regulation of glucose and fatty acid oxidation, and played an important role in obesity and diabetes. The researchers hope to reduce diabetes-related deaths by analyze the structure of receptors AdipoR1 and AdipoR2.
It is known that type 1 diabetes and type 2 diabetes in vivo adiponectin levels is relatively low. Studies also show that this hormone can improve glucose intolerance in mice. In addition, shortly before the development of small molecule called AdipoRon capable of simulating adiponectin, adiponectin activation in genetically obese mice receptors, improve glucose intolerance and extend the life of mice.
Adiponectin receptors in mammals, plants, yeast and many other organisms are evolutionarily conserved and that means they have an important biological role. The researchers believe that understanding the mechanism of binding adiponectin receptors contribute to the design of new drugs target to these receptors.
SPring-8 is the world’s highest-energy third-generation synchrotron radiation source, Shigeyuki Yokoyama, Takashi Kadowaki and Toshimasa Yamauchi led the research team used the device to obtain a high-resolution crystal image of adiponectin receptors.
To their surprise, the adiponectin receptor is a new type of structure, and their transmembrane helix is completely different from G protein-coupled receptor and G protein-coupled receptor is currently the most commonly used drug development target. Further research also showed that adiponectin receptors in the integration of a zinc ion, by three histidine residues fixed. The researchers noted that the presence of the large cavity of unknown function of adiponectin receptors. Yokoyama speculated that they may be the inlet and outlet of the substrate, and receptor activity.
“We get a lot of interesting unexpected discovery by analyzing these two important evolutionarily conserved receptors. We believe that the new information adiponectin receptor structure can help us to further understand the relationship between structure and function. This study helps people develop adiponectin targeted receptor drugs, for type II diabetes and other obesity-related diseases for treatment. presence of zinc ions receptor structure makes us particularly interested in understanding the importance of it need to do more work, “Yokoyama said.