The global population consumes too much fructose, a sugar found in many ultra-processed foods like cookies and energy drinks. This excessive intake can lead to type 2 diabetes and fatty liver disease. A gut dysfunction may be to blame, according to a study by Professor Fernando Forato-Anhê from the Faculty of Medicine at Université Laval.
Using a mouse model, his team observed that excess fructose alters intestinal glucose sensors, another crucial form of sugar in the diet. "Normally, the gut detects glucose and adjusts its absorption capacity accordingly, but the disruption of this process leads to exaggerated absorption, resulting in glucose intolerance or prediabetes, as the body can't effectively remove excess glucose from the bloodstream to the tissues that need it," explains the researcher, who is also affiliated with the Quebec Heart and Lung Institute - Université Laval.
Their study identifies a new therapeutic target, as previous literature often assumed a defect in insulin sensitivity—the hormone that helps the body absorb glucose.
The scientists used two groups of mice: one fed only glucose and another whose diet included both glucose and excess fructose, mimicking human overconsumption of this sugar. The effects of excessive fructose were rapid.
A hormone at fault
The dysregulation appears to be caused by the hormone Glp2. In mice consuming high amounts of fructose, the team noted increased secretion of Glp2, which in turn boosts glucose absorption.
By blocking the receptor of this hormone, Glp2r, the scientists were able to prevent the harmful effects of fructose overconsumption—such as increased intestinal glucose absorption, the onset of glucose intolerance, and fatty liver disease. However, in humans, blocking the Glp2r receptor isn't as straightforward, as its activation may also play a beneficial role in maintaining intestinal barrier integrity, which protects against microbial invasion, warns Professor Forato-Anhê.
His team will explore therapeutic avenues related to the gut microbiota. The researcher mentions, for instance, using gut microbes that react to fructose. "They could 'bury' the excessive secretion of the Glp2 hormone, responsible for exaggerated glucose absorption leading to intolerance," explains the researcher, who is also affiliated with the Institute of Nutrition and Functional Foods.
Beyond treatment prospects, the findings could aid in disease diagnosis. "We showed that intestinal glucose absorption capacity increases before glucose intolerance appears. This could serve as an early biomarker to identify at-risk individuals and intervene more effectively." The researcher suggests using blood tests. "The intestinal glucose absorption test is already performed in humans—it would just need to be applied in a different context."
The study was published in the scientific journal
Molecular Metabolism and is featured on the cover of the March 2025 issue. The authors are Eya Sellami, Paulo Henrique Evangelista-Silva, Caio Jordão Teixeira, Khoudia Diop, Patricia Mitchell, and Fernando Forato Anhê.