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“Metformin Impairs Intestinal Fructose Metabolism”

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 pro...

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Detalles Bibliográficos
Autores principales: Tong, Wenxin, Hannou, Sarah A., Sargsyan, Ashot, Zhang, Guo-Fang, Grimsrud, Paul A., Astapova, Inna, Herman, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153158/
https://www.ncbi.nlm.nih.gov/pubmed/37131695
http://dx.doi.org/10.1101/2023.04.17.537251
Descripción
Sumario: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.