2021.9 Exclusive Report by Liberty Times: Diabetes May Be Curable! Academia Sinica Team's New Discovery Holds Potential to Replace Insulin
[translated from Chinese]
〔楊媛婷／Repoter. Taipei〕
The current situation where diabetes is considered incurable is set to be reversed! A team led by Dr. Wen-Ching Yang, a research fellow at the Agricultural Biotechnology Research Center of Academia Sinica, discovered through mouse experiments that Pdia4 (Protein Disulfide Isomerase) is responsible for regulating pancreatic beta-cells. By using the developed inhibitor, "PS1," to suppress Pdia4 activity, they can inhibit islet failure and reverse diabetes.
Dr. Yang stated that this marks the first novel diabetes target drug since the invention of insulin a century ago in 1921. The drug is scheduled to undergo a Phase I clinical trial at National Taiwan University Hospital early next year, with an estimated launch date in seven years.
According to statistics from the Health Promotion Administration (HPA), the prevalence of diabetes among adults in Taiwan is 9.8%, affecting over 2 million people nationwide. If the disease deteriorates to the point of insufficient insulin secretion, patients are relegated to lifelong insulin injections. Even with regular administration, insulin can only delay deterioration, and there are currently no drugs or treatments that can cure diabetes.
However, this situation is poised to change. Dr. Yang's team discovered that Pdia4 is mainly expressed in pancreatic beta-cells, and over-nutrition increases its expression in human and mouse islet cells. In mouse models of the disease, removing the Pdia4 gene was found to alleviate diabetes and islet failure in the mice, simultaneously lowering blood glucose, glycated hemoglobin (HbA1c), and Reactive Oxygen Species (ROS), and even increasing insulin secretion. This brings hope for the complete cure of diabetes. The team also found that the overexpression of Pdia4 exacerbates diabetes and beta-cell lesions in mice. The research indicates that Pdia4 increases ROS content by regulating the ROS production pathway in beta-cells, ultimately leading to beta-cell failure and diabetes.
The team not only found the pathogenesis mechanism of diabetes through Pdia4 but also discovered that an artificially synthesized Pdia4 inhibitor (PS1) can inhibit beta-cell failure and reverse diabetes. This indicates that Pdia4 is an entirely new target for diabetes drugs, and the inhibitor has a high potential for curing diabetes.
Dr. Yang further explained that inhibiting Pdia4 in the beta-cells can suppress beta-cell failure. Generally, the cause of diabetes stems from long-term excessive intake of food sugars and fatty acids, which creates metabolic stress upon entry into the body and causes beta-cells to express high amounts of Pdia4, eventually leading to beta-cell failure. In mouse trials, the artificially synthesized PS1 was shown to inhibit Pdia4 activity in beta-cells and possess a curative effect against diabetes. Dr. Yang believes that if this target drug is used in patients with early-to-mid-stage diabetes, where 30% to 50% of beta-cells still remain, it is likely to reverse human diabetes.
If the clinical testing of this drug is successful, it will be a first-in-class diabetes drug developed specifically for pancreatic beta-cells, marking a new milestone in the treatment of diabetes for humanity. Taiwan's annual National Health Insurance expenditure of 30 billion TWD on diabetes treatment could see improvement.
The research has been published in the authoritative international journal, EMBO Molecular Medicine.