Asprosin, a new hormone, for the treatment of diabetes?

Asprosin, a new hormone, for the treatment of diabetes?

Researchers identified two patients with the rare disorder neonatal progeroid syndrome (NPS) in 2013 (only a handful of patients had been described to have this disorder worldwide, and its cause was unknown). Both patients had lived their entire lives with this "mysterious" disorder and were invited both to the genetics clinic at Texas Children's Hospital for initial interviews and tests.

Using whole exome sequencing, the research team discovered the genetic mutation that appeared to be responsible for NPS. However, how that mutation resulted in the disorder was still unknown.

Taking this problem to the laboratory, the researchers were able to figure out that these mutations prevented the patients from generating a previously unknown hormone. This newly discovered hormone, named asprosin, appears to be generated by fat. It travels to the liver where it instructs the liver to release glucose into the blood stream. NPS patients with abnormally low levels of asprosin are unable to do this and display low blood glucose and insulin.

In the opposite direction, patients with obesity/diabetes who have high blood glucose and insulin display higher than normal levels of asprosin. Using this information, the researchers determined that they could develop an antibody against it, and use that antibody to neutralize asprosin, a process called immunologic sequestration. This way they could potentially reduce the amount of glucose released by the liver, resulting in the pancreatic cells needing to release less insulin.

"We began to wonder, could this be a way to treat diabetes?" said the author.To test this concept, they treated diabetic mice with this antibody and found that even a single dose of the antibody worked well to reduce their insulin levels back toward the normal range. When such mice were treated for a longer period of time, their insulin resistance completely normalized.

"This result brought us full circle. We started with an extremely rare genetic disorder, and using information learned from those patients, discovered a new hormone that can be targeted to treat a different disease that affects many more people. If humans with diabetes respond the same way to the asprosin antibody that diabetic mice do, this discovery could result in a new treatment for diabetes, which affects millions of people," said the author.



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