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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 specifically 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 specifically so as to minimize side effects.

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