2021.9 CNA News: Diabetes May Be Curable - Academia Sinica Discovers Potential Inhibitor
[translated from Chinese]
2021/9/23 12:51 (Updated 9/23 13:21)
(Taipei, September 23, CNA Reporter Wu Xin-Yun) Taiwan sees nearly 10,000 deaths annually due to diabetes. Academia Sinica has discovered that Protein Disulfide Isomerase regulates pancreatic beta-cell failure and diabetes. Mouse experiments show that its knockout can cure diabetes, and its inhibitor holds the potential to cure the disease, with the research published in an international journal.
For many years, diabetes has remained incurable, primarily due to the loss of beta-cell count and function during the disease progression, leaving patients to rely on lifelong insulin injections for survival. According to the Health Promotion Administration, there are over 2 million diabetic patients nationwide, with numbers continuously increasing at a rate of 25,000 per year.
The research team led by Dr. Wen-Ching Yang from the Academia Sinica's Agricultural Biotechnology Research Center recently released its latest findings: Protein Disulfide Isomerase (Pdia4) is mainly expressed in beta-cells, and over-nutrition increases its expression in human and mouse beta-cells.
In mouse models of the disease, the Pdia4 gene knockout was found to alleviate diabetes and islet failure, simultaneously lowering blood glucose, glycated hemoglobin (HbA1c), and Reactive Oxygen Species (ROS), increasing insulin secretion, and even curing diabetes. Conversely, the overexpression of Pdia4 exacerbated diabetes and beta-cell lesions in mice.
Dr. Yang's team found that this mechanism shows Pdia4 causes beta-cell failure and diabetes by regulating the ROS production pathway within beta-cells and increasing ROS content. They also discovered that the Pdia4 inhibitor (a lead compound of PS1) can inhibit beta-cell failure and reverse diabetes.
Dr. Yang stated that the research team has identified Pdia4 as an entirely new drug target for diabetes, and its inhibitor holds the potential to cure the disease. With support from the Ministry of Science and Technology and other programs, preclinical trials have been completed. Phase I clinical trials are expected to be conducted in Taiwan in January next year (2022), though it will take at least seven years for the drug to complete clinical trials and reach the market.
Academia Sinica noted that the research has been published in the international journal, EMBO Molecular Medicine. (Editor: 管中維 ) 1100923