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"Metformin Impairs Intestinal Fructose Metabolism"
Wenxin Tong1, Sarah A Hannou1,2, Ashot Sargsyan1
1Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Objective:
To 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.
Results:
Metformin 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.
Conclusion:
Metformin reduces intestinal fructose metabolism, and this is associated with broad-based changes in intestinal enzyme and protein levels involved in sugar metabolism indicating that metformin's effects on sugar metabolism are pleiotropic.
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