Food and Behaviour Research

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Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance

Wu Y, Wong CW, Chiles EN, Mellinger AL, Bae H, Jung S, Peterson T, Wang J, Negrete M, Huang Q, Wang L, Jang C, Muddiman DC, Su X, Williamson I, Shen X. (2022) Cell Metabolism  S1550-4131(22)00189-9. doi: 10.1016/j.cmet.2022.05.007. Online ahead of print. 

Web URL: View this and related abstracts via PubMed here



  • High-fat diet increases fructose metabolism in the small intestine
  • Intestinal fructose metabolism releases glycerate into circulation
  • Circulating glycerate induces pancreatic islet cell damage
  • Circulating glycerate induces glucose intolerance


Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes.

Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the small intestine.

Here, we report that
dietary fat enhances intestinal fructose metabolism, which releases glycerate into the blood.

Chronic high systemic glycerate levels induce
glucose intolerance by slowly damaging pancreatic islet cells and reducing islet sizes.

Our findings provide a link between dietary fructose and diabetes that is modulated by dietary fat.


The strong association between modern, western-type diets and rates of Type 2 diabetes and related metabolic conditions (incuding obesity) is well known.

A subsequent dramatic rise in rates of Type 2 diabetes, and obesity, has been seen in every country that has adopted the 'Standard American Diet (SAD) diet - which is now most countries.  And this diet is high in BOTH sugar AND fat (from industrially-produced seed oils) owing to the dominance of 'ultra-processed foods'.

Researchers have now discovered a previously unknown mechanism - by which the harmful effects of fructose are amplified by high circulating fat levels, causing damage to insulin-producing cells in the pancreas.

This mechanism provides key evidence to support a cause-and-effect link between eating a 'fast food diet' (such as the typical burger, fries and sugary soft drink) - and developing Type 2 diatetes.

Read the associated news article on this important study here: