Anti-inflammatory drugs may reduce metabolic disease risk by inhibiting the sweet taste receptor

Past studies have shown that the human sweet taste receptor conveys sweet perception in the mouth and may help regulate glucose metabolism throughout the body. At the same time, the anti-inflammatory medications ibuprofen and naproxen are structurally similar to inhibitors of the sweet taste receptor and have been associated with metabolic benefits. Researchers at the Monell Chemical Senses Center and Rutgers University have published a study in the British Journal of Pharmacology that indicates these drugs could be another way to reduce the risk of metabolic diseases by inhibiting the sweet taste receptor throughout the body.

What we discovered is that ibuprofen and naproxen inhibit activation of the sweet taste receptor in people, as well as in human cells. We determined that if ibuprofen and naproxen inhibit sweet taste by inhibiting the TAS1R2-TAS1R3 taste receptor response to sugars, this may affect glucose metabolism."

Paul AS Breslin, PhD, senior author and Monell Member 

In the team's cellular studies, ibuprofen reduced molecular signaling of sucrose and sucralose in human kidney cells made to express the sweet taste receptor. In addition, to mirror internal human physiology in the mouth, low concentrations of ibuprofen, about the same as human plasma levels after a typical dose taken at home, inhibited sweet taste and oral detection of glucose at concentrations about the same as post-meal blood sugar levels.

Connecting the dots

Long-term ibuprofen use has been associated with preserved metabolic function and reduced risk of metabolic diseases such as Alzheimer's, diabetes, and colon cancer. In addition to their anti-inflammatory properties, the team found that ibuprofen and naproxen also inhibit an important blood glucose receptor. In the team's human experiments, for example, when a participant rinses their mouth with ibuprofen, the perception of sweetness from a variety of sugars and sweeteners is reduced.

Evidence from other studies has also shown that ibuprofen and chronic disease risk reduction are intertwined. The most obvious situation, notes Breslin, is Type 2 diabetes – if you have increased blood sugar and take a lot of ibuprofen, your blood sugar decreases. The second is a decreased risk of diseases that involve glucose metabolism in specific tissues, like Alzheimer's and some cancers.

"Our study connects the two functions of TAS1R receptors as the gatekeepers of sugar intake and a downstream modulator of glucose metabolism," said Breslin, also a Professor of Nutritional Sciences at Rutgers University. "In this paper we show that ibuprofen does more than modulate inflammation. It is also a TAS1R2-TAS1R3 inhibitor – a receptor expressed in most metabolic regulatory tissues and organs." Much evidence exists from previous studies that if you inhibit TAS1R2-TAS1R3 receptors, metabolism can change.

"Our work is connecting the dots," said Breslin. "We are trying to say that when thinking about these inflammatory and metabolic diseases – like Alzheimer's and diabetes – if we manipulate the taste receptors expressed throughout the body, this may have significance for lowering glucose to decrease disease risk."

Other co-authors are Lauren Caronia and Peihua Jiang, both from Monell; and Emily C. Hanselman, Caroline P. Harmon, Daiyong Deng, and Sarah M. Sywanycz, all from the Department of Nutritional Sciences, Rutgers University.

This work was funded by National Institutes of Health National Institute on Deafness and Other Communication Disorders grants R01 014286 and R21 020365, as well as the New Jersey Hatch Project NJ14120.