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New progress in the study of anti-diabetic mechanism of metformin
In a new study, researchers in Canada and the United Kingdom found how first-line anti-type 2 diabetes drug metformin might help cells better harvest and use glucose. Their research may also explain other potentially beneficial effects of metformin in the prevention of multiple chronic diseases, including cancer. The relevant research results were published online in the Cell Journal on October 24, 2018, and the title of the paper is "Changes of cell biochemical states are revealed in protein homomeric complex dynamics".
To confirm that metformin appears to make cells appear to lack the necessary mineral iron, these researchers used a new method to simultaneously detect how all biochemical processes in a cell respond to the presence of a drug. They found that metformin had a global effect on the distribution of iron in the cells, leading to changes in important biochemical processes.
The new technology that made this discovery possible was developed in the laboratory of the main author of the paper, Stephen Michnick, professor of biochemistry at the University of Montreal, Canada. Michnick said, "If you want to know the role of a drug or any other molecule in the body, then you need to immediately study what it happens in the cell. There are several ways to do this, but we call it hdPCA. The method is simple to implement, easy to understand, non-invasive and inexpensive; it can be done in almost any laboratory." This method can be quickly deployed to predict and confirm how a drug affects cells and simultaneously identifies Unfavorable factors that may be present when introducing this drug into the human body.
Bram Stynen, the first author of the paper and biochemist at the University of Montreal, added, “We chose to use metformin, mainly because it is an interesting test case and there is no clear mechanism of action. The effect of metformin on iron homeostasis is One of the results of this study. It has been previously speculated that there is a link between iron metabolism and diabetes, but no one has ever confirmed that the specific anti-diabetic effect of metformin in living cells is related to iron homeostasis." British Francis-Kerry Markus Ralser, a biochemist at the Institute, added, "This makes sense -- glucose metabolism is likely to have evolved from iron-dependent chemical reactions -- and this chemical relationship has not disappeared during evolution."
Further research in cells and animals is needed to determine the importance of the iron deficiency mimetic effect of metformin on glucose metabolism and how it might be better to use this mechanism to improve diabetes treatment.
Reference: Bram Stynen et al. Changes of cell biochemical states are revealed in protein homomeric complex dynamics. Cell, Published Online: 24 October 2018, doi:10.1016/j.cell.2018.09.050.