TAIPEI (Taiwan News) — Taiwanese scientists have discovered a key mechanism that causes diabetes and developed a new drug treatment that could "fully reverse" the disease, according to reports.
Diabetes has been shown to be caused by the loss and function of Beta cells (β-cells) in pancreatic islets, which are regions of the pancreas that contain hormone-producing cells. Yang Wen-chin (楊文欽) and his team at Academia Sinica's Agricultural Biotechnology Research Center (ABRC) have discovered through experiments on mice that the protein-coding gene, Pdia4 (Protein Disulfide Isomerase Family A Member 4), is responsible for the destruction of β-cells and that inhibiting this gene can prevent and even reverse the loss of such cells.
In the study, Academia Sinica scientists found that in mice the presence of Pdia4 led to the death of β-cells, their dysfunction, and the production of aberrant reactive oxygen species (ROS). They found that Pdia4 works with its downstream partners, Ndufs3 and p22phox, to increase ROS generation in the mitochondria and cytosol of β-cells, leading to their failure and the progression of diabetes.
When scientists introduced the Pdia4 inhibitor, 2-β-D-glucopyranosyloxy1-hydroxytrideca 5,7,9,11-tetrayne (GHTT), they found that it interfered with the interaction between the gene with its partners, reduced ROS production, and ameliorated β-cell failure. The result of this ablation of Pdia4 was found to alleviate diabetes in mouse models.
Furthermore, the scientist found that this ablation method alone or in combination with food reduction could "fully reverse diabetes." The researchers believe that the reversal of diabetes in the mice was the result of reduced β-cell deaths "and/or replenishment of β-cells."
Based on the study, Yang suggests that Pdia4 can be used as a diagnostic target for diabetes, while its inhibitor GHTT can be employed as a therapeutic to treat the disease. Yang was sited by CNA as stating that preclinical studies have been completed with the support of the Ministry of Science and Technology. Phase I clinical trials are slated to begin in Taiwan in January of next year, and it is estimated that it will take at least seven years for the drug to complete clinical trials and reach the market.
According to the Health Promotion Administration statistics, there are approximately 2 million people who suffer from diabetes in Taiwan. New cases increase at a rate of 25,000 per year.
