2023-06-27 12:45:32
There are still many unknowns about the mechanism of action of metformin, the most prescribed drug to treat diabetes mellitus, better known as type 2 diabetes.
Now, a research review study demonstrates how metformin is able to interact with the liver and intestine to reduce circulating glucose levels.
The team that carried out the study is made up of, among others, Emma Barroso and Manuel Vázquez-Carrera, from the University of Barcelona (UB) and the Institute of Biomedicine of the UB (IBUB). Vázquez-Carrera, a professor, also works at the Sant Joan de Déu Research Institute (IRSJD) in Barcelona, and the Biomedical Network Research Center for Diabetes and Associated Metabolic Diseases (CIBERDEM), in Spain.
Type 2 diabetes is a metabolic disease in which there is an excessive amount of glucose in the blood, due to the body’s inability to respond adequately to the actions of insulin—a process known as insulin resistance—or to produce this hormone. . To fight against this disease, metformin is usually used, an orally administered drug that reduces the contribution of glucose in the blood (hypoglycemic agent) and improves its peripheral circulation.
“Historically, it has been thought that the main site of action of metformin is the liver, but the most recent findings confirm that it also has notable effects in the intestine,” says Vázquez-Carrera, head of the Pharmacological Targets in Inflammation Research Group. and Metabolic Diseases of the UB. “For this reason,” he adds, “most of the more advanced studies focus on the two organs in which the actions of metformin seem to be most important: the liver and the intestine,” he explains.
Professor Manuel Vázquez-Carrera, from the Faculty of Pharmacy and Food Sciences of the University of Barcelona and the Institute of Biomedicine of the UB (IBUB). (Photo: University of Barcelona. CC BY)
Last year, a team verified that, in the liver, metformin is capable of increasing the levels of let-7 microRNA, a signaling molecule in various physiological functions. This pathway reduces hepatic glucose production, which is the process that most contributes to the rise in glucose in patients with type 2 diabetes. The study was published in the academic journal PNAS.
“These results open up the possibility of activating the expression of the let-7 microRNA, which is reduced in diabetic states, as a new strategy for the treatment of diabetes mellitus”, indicates Vázquez-Carrera.
In parallel, the effects of metformin on the intestine have also been described. In one of the most recent studies, another team has shown that metformin activates the conversion of glucose to lactate and acetate in the intestine (PNAS, 2023). “These two metabolites reach the liver through the portal vein and trigger processes that reduce hepatic glucose production. Therefore, metformin establishes a communication (crosstalk) between the intestine and the liver that contributes to its antidiabetic effects”, points out the researcher.
It should be remembered that the team led by Manuel Vázquez-Carrera also determined that metformin requires the presence of growth differentiation factor 15 (GDF15) to activate its main pharmacological target (AMPK) and have antidiabetic effects (Pharmacological Research, 2022).
“In summary, all the new studies reviewed help to resolve the unknowns that remain and provide data to understand how metformin reduces hepatic glucose production, which is the main antidiabetic effect of this drug.”
The review of study results is entitled “Striking a gut–liver balance for the antidiabetic effects of metformin”. And it has been published in the academic journal Trends in Pharmacological Sciences. (Source: University of Barcelona)
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