Could study of FOXO transcription factor one day lead to new therapies?
The treatment of diabetes mellitus is a common topic that has been discussed in many studies. The cost of treatments could be a huge burden for patients and their families, and the World Health Organization estimates that diabetes mellitus will be the seventh leading cause of death by the year 2030. Since it is a devastating disease that can involve any system of the body, patients and their physicians focus on the control of blood glucose levels to prevent further complications.
Because of insulin resistance and pancreatic beta cell failure in type 2 diabetes, the current treatment options of T2M are aimed at increasing insulin sensitivity and reducing blood glucose levels in the patient’s body. A review study published in Diabetologia investigated whether forkhead box protein O (FOXO) transcription factor could help people to understand the pathophysiology of diabetes, and potentially lead to the design of new therapies.
This study included many biological functions of FOXO in metabolism, such as the regulation of hepatic glucose production, liver lipids, and bile acids. They focused on the role of FOXO in the hepatic insulin resistance and beta cell failure.
In the regulation of hepatic glucose production, FOXO1 can drive the G6pc gene, which is encoding glucose 6-phosphatase, and glucose 6-phosphatase is rate-limiting enzyme in glycogenolysis, and hepatic insulin resistance can be correlated with excessive FOXO activity. The study also concludes hepatocyte FOXO1 can be inactivated by insulin, and then G6PC expression is repressed. At the same time, FOXO also linked to beta cell failure. FOXO nuclear translocation can indicate beta cell stress, and loss of FOXO can lead to loss of insulin.
In conclusion, the researchers hope a new treatment of diabetes can be derived by understanding of the functions of FOXO in the pathophysiology of diabetes.
- This review study investigated whether forkhead box protein O (FOXO) transcription factor could help people to understand the pathophysiology of diabetes.
- FOXO is correlated with the hepatic insulin resistance and beta cell failure.
- The researchers hope the new treatment of diabetes can be derived by understanding of the functions of FOXO.
Researched and prepared by Jennifer Zahn, Doctor of Pharmacy Candidate University Of South Florida College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE
Pajvani UB, Accili D. The new biology of diabetes. Diabetologia (2015) 58: 2459-2468. Published online: 7 August 2015