Light-activated diabetes drug may provide safer, more targeted treatment

Researchers have demonstrated a drug delivery system for diabetes that is activated by blue light to precisely signal the release of insulin, according to a study published online April 5, 2016 in the German journal Angewandte Chemie (Applied Chemistry).

In the past 10 years, incretin mimetics have revolutionized the treatment of type 2 diabetes, noted David Hodson, BVSc, PhD, of the Institute of Metabolism and Systems Research at the University of Birmingham, in Birmingham, UK.

“The challenge now is to make such interventions more targeted,” he said. “At the moment, the approach is equivalent to using a sledgehammer to crack a nut.”

Although the incretin mimetics effectively stimulate insulin release by inhibiting the glucagon-like peptide 1 (GLP-1) receptor, newer research has discovered a “back door” allosteric site on the GLP-1 receptor that could allow more selective and targeted action for more effective anti-diabetic drugs with fewer side effects. However, the allosteric site is too small for the current incretin mimetics.

To solve this problem, Dr. Hodson—along with Dirk Trauner, PhD, and Johannes Broichhagen, PhD, at Ludwig Maximilian University in Munich, Germany—used synthetic chemistry, biology, and high-throughput screening to produce a novel anti-diabetic drug that can be activated and precisely controlled with blue light.

Their new drug, PhotoETP, is composed of the allosteric modulator BETP, which is susceptible to ultraviolet and blue light. The scientists then “installed” azobenzene onto BETP to protect and stabilize it from the harmful effects of UV and blue light.

Next, they experimented with PhotoETP and found that the structure needed to be twisted to fit into the allosteric site. The researchers then applied blue light to the cells, which untwisted and extended the structure and allowed it to activate GLP-1 signaling to induce insulin secretion.

With this information, a new generation of light-activated anti-diabetics can now be produced that allow better control over blood glucose levels with fewer side effects, the researchers predicted.

“By advancing our understanding of receptors in cells, we can design more efficient drugs and reduce the risk of side effects,” Dr. Hodson said. “Light-activated technologies that change the shape of drugs are really interesting, non-invasive ways of getting the treatment to the right place at the right time.”