UCR Involved in Discovery of Diabetes Fighting Molecule

University of California, Riverside Assistant Professor of Bioengineering, Jiayu Liao played a pivotal role in the discovery of a small molecule that has been shown to control diabetes in mice and may pave the way to the development of easier treatment for adult-onset diabetes.

This discovery was a collaboration between Liao at UC Riverside's Bourns College of Engineering and a team in the National Center for Drug Screening, Shanghai, which is part of the Chinese Academy of Science.

This key molecule, identified as Boc5, can stimulate insulin function in response to high levels of glucose as well as reduce body weight by 20 percent. The discovery of this molecule that stimulates the production of the intestinal hormone glucagon-like peptide1 (GLP1), which metabolizes glucose, has been an extremely difficult goal for researchers in both academics and the pharmaceutical industry.

Boc5 is the first small molecule activator for Class B GPCRs, which regulate hormones in many human physiological processes and are major targets for pharmaceutical companies. This discovery opened new revenue possibilities to support future research into small molecule interaction with Class B GPCRs in the future.

In the study, Liao and his colleagues were looking for ways to sensitize sugar-metabolizing insulin by stimulating production of GLP1. Synthetic versions of this peptide have proven effective but of short duration so it had been abandoned by drug researchers.

However, after Liao and his colleagues screened a library of more than 48,000 natural and synthetic compounds, they identified a molecule, Boc5, which mimics glucagon-like peptide1 in the blood leading to increases in insulin secretion in laboratory cultured rat pancreatic cells when exposed to high glucose levels. The molecule also worked when administered by injection and orally in experiments with laboratory mice.

Thus Boc5 behaved as full GLP1 mimic, both in the test tube and in the laboratory mice, the researchers reported in an article that appeared in the Jan. 16 edition of the Proceedings of the National Academies of Science titled “A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice.”

The fact that the molecule also lowered appetite and promoted weight loss in mice, holds out the promise it may fuel more exploration of orally available insulin sensitizing drugs that can be used to control diabetes and obesity, the article’s authors wrote.

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Ricardo Duran EurekAlert!

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