Professor of Chemistry and Chemical Biology David Liu and Associate Professor of Chemistry and Chemical Biology Alan Saghatelian, describe the approach of using a newly discovered compound to inhibit insulin degrading enzyme (IDE). Inhibiting IDE in mice, they show, elevates insulin levels and promotes insulin signaling in vivo. The discovery of the new compound, and tests demonstrating its efficacy in mice, are outlined in a paper in Nature.
"This work validates a new potential target for the treatment of diabetes," Liu said. "What we show is that inhibiting IDE in an animal can improve glucose tolerance under conditions that mimic the intake of a meal if you administer this compound beforehand."
For decades, researchers said, insulin-based diabetes treatments consisted of three main strategies - inject insulin into diabetics, provide drugs that stimulate insulin secretion, or administer drugs that make the body more sensitive to insulin.
"What's been missing has been the ability to regulate the degradation of insulin," Saghatelian said. "The technological leap we've made was in identifying a molecule that allows that to happen. This opens up a new avenue to control insulin signaling in vivo."
Researchers were also able to show that the new compound remained active in the body, and experiments with mice showed that it was able to help regulate blood sugar levels.
"To validate that this strategy - of slowing the degradation of insulin - is actually therapeutically useful, we have to show that this compound can transiently inhibit the target, and show that it has a benefit in animals," Liu said. "That is what we demonstrate in this study."
In addition to pointing the way toward a new way to treat diabetes, researchers uncovered new information about how IDE works in the body.
"To develop a drug requires a number of additional tests and developments," he said. "But this work validates IDE as a new target for the treatment of diabetes, and it provides experimental tools that can be used to develop this compound further into potential therapeutic leads."
"What this paper has done is given a proof of concept that targeting this protein is the way to go," Saghatelian said. "To make the leap from this molecule to a drug, there are other factors that need to be optimized, but we've hung the carrot out there for the pharmaceutical industry and other labs to start looking at IDE as a potential target for treating diabetes, and to push through the remaining obstacles that are there. We've shown it's worth the effort to look into this more deeply, and hopefully what we've done is opened people's eyes to IDE as a valid therapeutic target."
- This new compound delays the breakdown of insulin
- It was also able to show better glucose control in mice
- Research opens the door to develop a new treatment paradigm
Journal of Consumer Research, May 2014.Researchers from Stony Brook University, the Albert Einstein College of Medicine, University of California Irvine and the University of Chicago contributed to the research.