U.S. Department of Health and Human Services

Protein on Surface of Beta Cells Is Possible Type 2 Diabetes Drug Target

​Researchers discovered that a protein found on the surface of insulin‑producing beta (β) cells in the pancreas may be an attractive drug target to prevent or treat type 2 diabetes. In type 2 diabetes, β cells do not release enough insulin to maintain healthy blood glucose levels. This defect is due to impairments in β cell function combined with reduced numbers of β cells (referred to as β cell mass). Scientists examined whether turning on (activating) a protein—called a Gq
‑coupled receptor—found on the surface of β cells would have an effect on β cell mass or function in mice. A related protein, a Gs‑coupled receptor, is already the target of type 2 diabetes drugs in humans, so the researchers wanted to determine if the Gq‑coupled receptor could also be a potential drug target. Like the G s form of the protein, the Gq form is found on many different cell types. Thus, to study the Gq form in β cells only, they used an experimental mouse model 
they had previously generated, which made a “designer” Gq‑coupled receptor speciically in β cells. The designer receptor could be activated by giving the animals a compound that was otherwise biologically inert. 

The scientists discovered that chronically activating the designer Gq‑coupled receptor with the compound resulted in a robust increase in the animals’β cell mass and function. This was associated with increased expression (turning on) of several genes known to be involved in promoting β cell development or maintaining normal β cell function. Activating the receptor prevented the animals from developing diabetes induced by a toxin that destroys a large percentage of β cells. It also prevented the metabolic defects seen when mice eat a high‑fat diet. These results suggest that Gq‑coupled receptors play an important role in regulating β cell function and blood glucose levels in mice. If they play a similar role in humans, they would be attractive targets for drug development to combat type 2 diabetes. Because the receptors are found on other cell types, therapeutic approaches would need to activate receptors found on β cells speciically so as to minimize side effects. 

Jain S, Ruiz de Azua I, Lu H, White MF, Guettier JM, and 
Wess J. Chronic activation of a designer Gq
‑coupled receptor 
improves β cell function. J Clin Invest 123: 1750‑1762, 2013.