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Alanine Shown to Support Glucose Metabolism

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According to new research from the Joslin Diabetes Center (Boston, MA), the amino acid alanine alters energy metabolism in the cell, creating a short-term drop in glucose levels.

In the mouse study, researchers sought to identify what nutrients would activate AMP kinase (AMPK), an enzyme in cells that is activated in response to exercise or when nutrients are low. AMPK then turns on genes that increase energy production in the cells. “AMPK is a good thing, and it also can be activated by a variety of treatments for Type 2 diabetes, such as metformin,” said co-author Mary-Elizabeth Patti, MD, a researcher in Joslin’s Section on Integrative Physiology and Metabolism.

The reserachers tested several amino acids in rat liver cells (the liver is a crucial organ in glucose metabolism) and found that alanine was the one amino acid that was consistently able to activate AMPK.

The researchers then confirmed that AMPK was producing normal metabolic effects after alanine activation. Additionally, the activation could be seen in human and mouse liver cells as well as rat liver cells and was present with either high or low levels of glucose in the cells.

Additionally, the Joslin team orally administered alanine to mice after which, their levels of AMPK increased. Further, if mice consumed alanine before they received a dose of glucose, their resulting blood glucose levels were significantly lower. And while glucose metabolism often behaves quite differently in lean mice than in obese mice, this mechanism was seen in both groups of mice.

Following up, the Joslin team found that the glucose lowering didn’t seem to be driven by increases in insulin secretion or decreases in secretion of glucagon, a hormone that increases glucose. Instead, AMPK was boosting glucose uptake in the liver and decreasing glucose release. Further experiments in cells demonstrated that the activated enzyme was altering the Krebs cycle, a central component of cell metabolism.

“Alanine may be a potential way to modify glucose metabolism,” Patti concluded. “Our study shows that it’s possible we can use specific nutrients, in this case amino acids, to change metabolism in a cell, and these changes in metabolism can change how cells take up and release glucose in a beneficial way.”


Adachi, et al. “l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism.” Molecular Metabolism, 2018; DOI: 10.1016/j.molmet.2018.08.002.