Wisconsin Alumni Research Foundation

Therapeutics & Vaccines
Therapeutics Vaccines
E-Prostanoid Receptor, Ptger3, As A Novel Anti-Diabetic Therapeutic Target
WARF: P110240US02

Inventors: Mark Keller, Alan Attie, Michelle Kimple

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a method to increase insulin secretion from beta cells by normalizing the activity of the Ptger3 gene.
Normally, digested food can be absorbed into the bloodstream in the form of sugars like glucose, which then signals pancreas beta cells to secrete more insulin. This insulin is needed to help the glucose molecules enter cells.

Type 2 diabetes mellitus (T2D) is a disease in which a person has high blood sugar because the body resists the glucose-lowering effects of insulin and beta cells fail to produce enough insulin. More than 18 million Americans have been diagnosed with T2D, at an annual cost of $174 billion. Complications from the disease are the third leading cause of death in the United States.

Treatment has focused on increasing the production of a signal-relaying molecule called cAMP. This molecule in turn boosts insulin secretion by helping beta cells grow and survive. Some agents used to increase cAMP levels target hormonal pathways that activate a necessary adenylate cyclase (AC) enzyme. Unfortunately, many patients do not respond to such treatments.
The Invention
UW–Madison researchers have discovered an additional target for diabetic therapy. The gene, known as Ptger3, is over-expressed in diabetics. It encodes a receptor called EP3 that negatively impacts insulin secretion from beta cells. When that activity is suppressed, secretion can be elevated to healthy levels.

Their discovery may be used to develop a new pharmaceutical for boosting insulin secretion from beta cells. To do this, the pharmaceutical would work on two fronts to increase cAMP production. It would include a compound (like sitagliptin) that directly or indirectly activates AC, as well as a compound that blocks EP3 activity. Such an EP3-specific antagonist could be the commercially available agent L-798,106.
  • Treating and preventing type I and type II diabetes
Key Benefits
  • Normalize insulin production to non-diabetic levels
  • Could prevent onset of diabetes
  • Since EP3 expression and activity are elevated only in response to diabetes, a drug inhibiting the Ptger3 gene should be disease-specific.
Stage of Development
The researchers have shown in both mice and humans that treating diabetic islet cells with a Ptger3 antagonist can enhance insulin secretion.

The development of this technology was supported by WARF Accelerator. WARF Accelerator selects WARF's most commercially promising technologies and provides expert assistance and funding to enable achievement of commercially significant milestones. WARF believes that these technologies are especially attractive opportunities for licensing.
Additional Information
For More Information About the Inventors
  • Kimple et al. 2013. The Prostaglandin E2 Receptor, EP3, is Induced in Diabetic Islets and Negatively Regulates Glucose- and Hormone-Stimulated Insulin Secretion. Diabetes. 62, 1904-1912.
For current licensing status, please contact Rafael Diaz at [javascript protected email address] or 608-960-9847