Glycerate from intestinal fructose metabolism induces islet cell damage and 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 dietar...

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Published in:Cell metabolism 2022-07, Vol.34 (7), p.1042-1053.e6
Main Authors: Wu, Yanru, Wong, Chi Wut, Chiles, Eric N., Mellinger, Allyson L., Bae, Hosung, Jung, Sunhee, Peterson, Ted, Wang, Jamie, Negrete, Marcos, Huang, Qiang, Wang, Lihua, Jang, Cholsoon, Muddiman, David C., Su, Xiaoyang, Williamson, Ian, Shen, Xiling
Format: Article
Language:English
Subjects:
Blood Glucose
diabetes
Diabetes Mellitus, Type 2
Diet, High-Fat - adverse effects
dietary fat
Dietary Fats - pharmacology
fructose
Fructose - metabolism
Glucose - metabolism
glucose intolerance
Glucose Intolerance - metabolism
glycerate
Humans
insulin
Insulin - metabolism
intestine
islet cell
Islets of Langerhans - metabolism
metabolism
western diet
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Summary: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. [Display omitted] •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 has been linked to metabolic syndromes such as diabetes. Wu et al. discovered that fructose metabolism in the small intestine releases glycerate into the blood circulation, which damages pancreatic islet cells and induces glucose intolerance. Dietary fat further elevates intestinal fructose metabolism and resulting circulating glycerate levels, supporting the long-term effect of western diet on exacerbating metabolic syndromes.
ISSN:1550-4131
1932-7420
1932-7420
DOI:10.1016/j.cmet.2022.05.007