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bioRxiv · 10.1101/2023.04.17.537251

Metformin Impairs Intestinal Fructose Metabolism

Tong, W.·Hannou, S. A.·Sargsyan, A.·Zhang, G.-F.·Grimsrud, P. A.·Astapova, I.·Herman, M. A.
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Abstract

ObjectiveTo investigate the effects of metformin on intestinal carbohydrate metabolism in vivo. Method: Male mice preconditioned with a high-fat, high-sucrose diet were treated orally with metformin or a control solution for two weeks. Fructose metabolism, glucose production from fructose, and production of other fructose-derived metabolites were assessed using stably labeled fructose as a tracer. ResultsMetformin treatment decreased intestinal glucose levels and reduced incorporation of fructose-derived metabolites into glucose. This was associated with decreased intestinal fructose metabolism as indicated by decreased enterocyte F1P levels and diminished labeling of fructose-derived metabolites. Metformin also reduced fructose delivery to the liver. Proteomic analysis revealed that metformin coordinately down-regulated proteins involved carbohydrate metabolism including those involved in fructolysis and glucose production within intestinal tissue. ConclusionMetformin reduces intestinal fructose metabolism, and this is associated with broad-based changes in intestinal enzyme and protein levels involved in sugar metabolism indicating that metformins effects on sugar metabolism are pleiotropic. HighlightsO_LIMetformin decreases intestinal fructose absorption, metabolism, and fructose delivery to the liver. C_LIO_LIMetformin reduces intestinal glucose production from fructose-derived metabolites. C_LIO_LIMetformin reduces protein levels of multiple metabolic enzymes involved in fructose and glucose metabolism in intestinal tissue. C_LI

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Tong, W., Hannou, S. A., Sargsyan, A., Zhang, G.-F., Grimsrud, P. A., Astapova, I., Herman, M. A.. 2023-04-18. Metformin Impairs Intestinal Fructose Metabolism. https://doi.org/10.1101/2023.04.17.537251

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