Liver metabolism discovery suggests potential new targets for diabetes treatment
New research has overturned the conventional view of what the liver does after a meal and suggests a backup pathway that governs glucose metabolism, according to the Perelman School of Medicine at University of Pennsylvania.
With each meal, insulin turns off glucose production in the liver. The “textbook” model of liver metabolism claims that a protein called Akt in the liver is absolutely required for proper insulin signaling.
However, the Penn researchers found that the livers of insulin-resistant mice lacking the Akt protein responded normally after a meal. The research team hypothesized that a backup pathway exists in the liver that governs glucose metabolism.
The researchers believe that insulin is working on other tissues' receptors and also communicates with the liver before and after a meal. Previous studies have shown that the brain has insulin receptors as well and that a pathway through the nervous system may exist.
Researchers surmise that the backup pathway has been difficult to see because the liver loses its ability to respond to outside signals when insulin signaling in the liver is disrupted.
The study found that the insulin-resistant mice have another gene, Foxo, that is turned on all the time. This keeps glucose production turned on because the liver believes that the body is fasting.
The scientists hypothesize that in the body's normal state, Foxo is off most of the time. Foxo is inappropriately activated in a diabetic state. They believe that Foxo prevents the liver from responding to the brain's signal to start or stop glucose production.
The researchers currently are conducting tests to prove this hypothesis.
These results suggest potential new pathways to target for type 2 diabetes treatment, according to the medical school.
A paper on the study appears online in Nature Medicine.
The hormone insulin helps the body use or store the blood glucose it gets from food, according to American Diabetes Association. In people with type 2 diabetes, the body makes insulin but it does not respond well to it. People living with type 2 diabetes may need diabetes medication or insulin shots to help their bodies use glucose for energy.
Source: University of Pennsylvania, American Diabetes Association