The Inhibition of GABA Production in the Liver Restored Insulin Sensitivity within Days

The accumulation of fat in the liver impairs its nerves which prevents the proper transmission of signals to the brain, which leads to the disruption of insulin regulation.



Type 2 diabetes affected 108 million people worldwide in 1980, according to figures from the World Health Organization. By 2014, that figure had nearly quadrupled: 422 million people were affected. Faced with these growing numbers, the scientific community is working to find new treatments, as the only drugs currently available only combat the symptoms. In the journal Cell Reports, two studies present a new avenue for the treatment of diabetes.

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What is the relationship between obesity, liver fattening, and type 2 diabetes?

For nine years, Benjamin Renquist, one of the authors of this study, and his team have been working on the links between obesity, fatty liver disease (FLD), and different types of diabetes. “Obesity is considered one of the causes of type 2 diabetes, and we have known for some time that the amount of fat in the liver increases with obesity,” he explains. As liver fat increases, the risk of diabetes increases. This observation led him to believe that liver fat could be the cause of type 2 diabetes. “But how can fat in the liver make the body insulin resistant?” he asks.

Disrupted communication between the brain and the liver

An animal study allowed the researcher and his team to identify a neurotransmitter produced by the liver in cases of obesity, called GABA, for gamma-aminobutyric acid. GABA’s function is to reduce nervous system activity. “When the liver produces GABA, it reduces the activity of the nerves that go from the liver to the brain,” the researcher continued. In response, the central nervous system adapts and reduces glucose-regulating activity.

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Promising results

In a second part of the study, the scientists wanted to confirm these results by switching off GABA neurotransmitters in animals with type 2 diabetes. “the inhibition of GABA production restored insulin sensitivity within a few days,” explains Caroline Geisler, who was responsible for this part of the study. Thus, in the long term, this has allowed for the reduction of food the animals consumed which made them lose weight. At the same time, the team found that people with insulin resistance had an above-average expression of genes related to GABA production in the liver. Renquist also added that this discovery is only the first step toward a therapeutic target. It will be several years before treatments are in a pharmacy near you.

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A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity



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