Nutrients may reduce blood glucose levels

October 10, 2018, Joslin Diabetes Center
Mary-Elizabeth Patti, MD, is investigator in the Section on Integrative Physiology and Metabolism at Joslin Diabetes Center and associate professor of medicine at Harvard Medical School. Credit: John Soares

Type 2 diabetes is driven by many metabolic pathways, with some pathways driven by amino acids, the molecular building blocks for proteins. Scientists at Joslin Diabetes Center now have shown that one amino acid, alanine, may produce a short-term lowering of glucose levels by altering energy metabolism in the cell.

"Our study shows that it's possible we can use specific nutrients, in this case , to change in a cell, and these changes in metabolism can change how take up and release in a beneficial way," says Mary-Elizabeth Patti, MD, an investigator in Joslin's Section on Integrative Physiology and Metabolism and senior author on a paper about the work recently published in Molecular Metabolism.

Performed in cells and in , her group's research began with an attempt to see what nutrients might activate a key protein called AMP kinase (AMPK), says Patti, who is also an associate professor of medicine at Harvard Medical School.

"AMPK is an enzyme in cells throughout the body that is activated when nutrient supplies are low, or in response to exercise," she explains. "AMPK then causes a lot of beneficial changes in the cell, turning on genes that serve to increase energy production. AMPK is a good thing, and it also can be activated by a variety of treatments for type 2 diabetes, such as metformin."

That raised a question for Patti and her colleagues: Could an amino acid switch on this beneficial enzyme?

The investigators began their study by testing many amino acids in rat liver cells (the liver is a crucial organ in ). "Alanine was the one amino acid that was consistently able to activate AMPK," Patti says.

The researchers then confirmed that AMPK was producing some of its usual 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.

Next, scientists gave alanine by mouth to mice and found that levels of AMPK rose in the animals. Moreover, if mice ate alanine before they received a dose of glucose, their resulting blood 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.

"All these data together suggest that amino acids, and specifically alanine, may be a unique potential way to modify glucose metabolism," Patti sums up. "If it eventually turns out that you can do that by taking an oral drug as a pre-treatment before a meal, that would be of interest. However, this is early-stage research, and we need to test the concept both in mice and ultimately in humans."

Explore further: Team uncovers secrets of our cellular 'energy sensor'

More information: Yusuke 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

Related Stories

Team uncovers secrets of our cellular 'energy sensor'

July 19, 2017
A scientific collaboration between researchers in Scotland and China has uncovered a new kind of 'energy sensor' in our cells, changing our understanding of how the body monitors glucose levels and switches on the supply ...

Exercise mimic molecule may help treat diabetes and obesity

July 27, 2015
Scientists from the University of Southampton have developed a molecule that acts as an exercise mimic, which could potentially help treat type 2 diabetes and obesity.

Study: Most-used diabetes drug works in different way than previously thought

January 6, 2013
A team, led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, ...

Animal study suggests common diabetes drug may also help with nicotine withdrawal

April 5, 2018
In a mouse study, a drug that has helped millions of people around the world manage their diabetes might also help people ready to kick their nicotine habits.

Apelin hormone injections powerfully lower blood sugar

November 4, 2008
By injecting a hormone produced by fat and other tissues into mice, researchers report in the November Cell Metabolism that they significantly lowered blood sugar levels in normal and obese mice. The findings suggest that ...

New regulator of liver metabolism discovered

September 29, 2017
Researchers from Charité - Universitätsmedizin Berlin have identified an enzyme that has a major effect on glucose utilization in liver cells. The enzyme, retinol saturase, helps these cells adapt to variations in glucose ...

Recommended for you

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Researchers give new insight to muscular dystrophy patients

December 13, 2018
New research by University of Minnesota scientists has revealed the three-dimensional structure of the DUX4 protein, which is responsible for the disease, facioscapulohumeral muscular dystrophy (FSHD). Unlike the majority ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.