Researchers have discovered a family of small molecules that increases insulin production in pancreatic β cells, and thus could be explored for potential use in diabetes therapy. They built on previous research showing that small molecules called isoxazoles (Isx) increase levels of the NeuroD1 protein in nerve cells and promote neuronal cell development. NeuroD1 is also a key regulator of β cell development and maturation, as well as insulin production in β cells. Therefore, the scientists tested whether Isx had an effect on β cells, which are found in clusters called islets in the pancreas. They examined human islets that had been in laboratory culture for a long period of time (2-12 months), during which they lose their ability to secrete insulin in response to glucose. They discovered that treating these human islets with Isx increased the levels of cellular factors that regulate insulin production, β cell function, and β cell development, resulting in enhanced insulin production. Experiments using mouse pancreatic cells in culture showed that treatment with Isx stimulated insulin secretion in response to glucose. These findings make Isx one of only a few known molecules that improves β cell function dramatically, although further research is needed before Isx or related molecules could be tested in people. Because impaired β cell function is central to both type 1 and type 2 diabetes, this research could potentially lead to new therapeutic approaches for both forms of the disease.
Dioum EM, Osborne JK, Goetsch S, Russell J, Schneider JW, and Cobb MH. A small molecule differentiation inducer increases insulin production by pancreatic β cells. Proc Natl Acad Sci USA 108: 20713-20718, 2011.