2021.9 EBC News: Diabetes May Be Curable! Academia Sinica Finds Key to Reversal, Set to Replace Insulin as New Target Drug
[translated from Chinese]
崔至雲 Reporter / Taipei
Diabetes has remained incurable for two millennia, primarily because patients lose the number and function of their pancreatic beta-cells during the disease progression. Consequently, diabetic patients are often forced to rely on insulin injections for survival.
The research team led by Dr. Wen-Ching Yang, a research fellow at the Academia Sinica's Agricultural Biotechnology Research Center, discovered that Protein Disulfide Isomerase (Pdia4) is responsible for regulating beta-cells. In mouse models of the disease, it was shown to inhibit islet failure and reverse diabetes, making it a promising new target for diabetes drugs in the future.
According to statistics from the Health Promotion Administration (HPA), over 2 million people in Taiwan suffer from diabetes. If the condition deteriorates to insufficient insulin secretion, they must be on insulin for life, as there are currently no available drugs or treatments that can cure diabetes.
Dr. Yang's team first discovered that Pdia4 is mainly expressed in beta-cells, and over-nutrition increases its expression in human and mouse beta-cells. In diabetic mouse models, the Pdia4 gene knockout was found to alleviate diabetes and islet failure, reduce blood glucose, glycated hemoglobin (HbA1c), and reactive oxygen species (ROS), and increase insulin secretion. More importantly, the Pdia4 gene knockout was found to cure diabetes. Conversely, Pdia4 overexpression exacerbates diabetes and beta-cell lesions in mice.
The study indicates that Pdia4 causes beta-cell failure and diabetes by regulating the ROS production pathway within beta-cells and increasing ROS content. Furthermore, the research found that the Pdia4 inhibitor (a lead compound of PS1) can suppress beta-cell failure and reverse diabetes.
Therefore, Dr. Yang explained, they identified Pdia4 as an entirely new drug target for diabetes, and its inhibitor holds the potential to cure the disease. PS1, a first-in-class small-molecule drug for diabetes, has completed preclinical trials. The research has been published in the authoritative international journal, EMBO Molecular Medicine.