It is estimated that more than 422 million people in the world have diabetes; by 2021 the cost burden of diabetes in the United States is on track to be $512 billion. Diabetes, characterized by elevated blood glucose (sugar) levels, results from either beta-cell malfunction (Type 2) or beta-cell demise after an autoimmune attack (Type 1). The hormone insulin, produced by pancreatic beta-cells, reduces circulating levels of glucose after a meal primarily by shuttling glucose to muscle and fat. Current strategies to treat diabetics include insulin injection, augmenting endogenous insulin secretion, increasing glucose absorption, or increasing glucose excretion. Hypoglycemic (low blood glucose) episodes after insulin injection are life threatening and this risk usually results in patients underdosing. Here we describe the discovery of a novel peptide hormone, we call ERSEQ08, present in human beta-cells, that can reduce blood glucose levels in mice. Importantly, this effect is independent of insulin action. Surprisingly, ERSEQ08 lowers blood glucose, in a glucose dependent manner, without causing hypoglycemia—thus overcoming one of the major setbacks with current diabetic treatments. While it is well known that pancreatic beta cells make Insulin, this new finding may represent a second system by which beta cells regulate glucose metabolism.
The potential to bypass insulin resistance presents a novel therapeutic paradigm to treat diabetes. As a biologic, this hormone may complement or replace some of the therapies used as the current standard of care in diabetes treatment. As an inroad into a novel signaling system controlling glucose homeostasis, this discovery has the potential to lead to a new kind of drug for diabetics.
Our main objectives using the Q-FASTR funds are: to test the activity of recombinant human ERSEQ08 protein to lower blood glucose levels in mice; to develop a cell-based assay to identify ERSEQ08’s mechanism of action; and, to find the minimal active fragment required for ERSEQ08’s function.