Target Discovery to Diabetes Therapy-TXNIP From Bench to Bedside With NIDDK.

Abstract

Diabetes is the most expensive chronic disease in the United States, with more than $400 billion in annual costs, and it affects more than 38 million Americans. While major advances in drug treatment have been made for type 2 diabetes (T2D) and the often-associated obesity, there are still no approved and effective medications targeting β-cell loss or islet dysfunction, which is one of the major underlying causes of both type 1 diabetes (T1D) and T2D. In addition, there are no oral medications for T1D approved in the United States more than 100 years after the discovery of insulin, and attractive therapeutic targets are only starting to emerge. As we celebrate the 75th anniversary of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), progress is finally being made in this area with NIDDK support. This mini-review follows the discovery of thioredoxin-interacting protein inhibitors as an example of a methodical approach to identify and develop an oral β-cell treatment for T1D. It further discusses how the initial molecular findings were translated into novel clinical treatment approaches that promote the patient's own islet health and β-cell function using drug repurposing as well as new drug discovery.