This year marks the centenary of the discovery of insulin, which transformed diabetes from a severe disease into a manageable condition. This centennial seems to bring new hope for patients as scientists have developed a new methodology promising more effective treatment for type 2 diabetes. In two recent studies published in the journal "Cell Reports," researchers from the universities of Arizona, Washington, Pennsylvania, and Northwestern identified a new target for treating type 2 diabetes.
Fatty Liver
Type 2 diabetes is 24 times more common than type 1 and is linked to rising obesity rates, necessitating new treatment methods, according to researchers at the University of Arizona, who believe the liver could be the key to innovation and the development of new treatments. Benjamin Rinkewist, an assistant professor at the College of Agriculture and Life Sciences at the University of Arizona and a member of the BIO5 Institute, expresses hope for providing more effective treatments for type 2 diabetes, stating, "We need another breakthrough."
Rinkewist's research lab aims to address obesity-related diseases, having spent the last nine years studying the relationship between obesity, fatty liver disease, and diabetes, particularly how the liver affects insulin sensitivity. Rinkewist notes: "Obesity is known to cause type 2 diabetes, and for a long time, we have known that fat in the liver increases with obesity. With increasing fat in the liver, the likelihood of developing diabetes also rises." He adds that this suggests liver fat may cause type 2 diabetes, but how does liver fat lead the body to resist insulin or cause the pancreas to produce excessive insulin?
Transaminase Enzyme
To solve this puzzle, Rinkewist and his colleagues focused on fatty liver and measured the neurotransmitters released by the liver in animal models of obesity to better understand how the liver communicates with the brain affecting metabolic changes seen in obesity and diabetes. Rinkewist explains: "We found that liver fat increases the release of the inhibitory neurotransmitter, gamma-aminobutyric acid, or 'GABA,' and then identified the pathway through which GABA is synthesized and the key enzyme responsible for its production, liver transaminase (GABA)."
GABA is a natural amino acid and the primary inhibitory neurotransmitter in the central nervous system, meaning it reduces nerve activity. The nerves provide a channel through which the brain communicates with the rest of the body. Rinkewist clarifies that this communication occurs not only from the brain to other tissues but also from tissues to the brain. He explains: "When the liver produces GABA, it reduces the activity of those nerves that extend from the liver to the brain. Thus, fatty liver, through GABA production, diminishes communication with the brain." The researcher adds: "This reduction is sensed by the central nervous system, which in turn alters the signals affecting glucose balance."
Animal Models
In an effort to determine whether increased GABA synthesis in the liver causes insulin resistance, Rinkewist's graduate students inhibited liver transaminase (GABA) in animal models of type 2 diabetes. Postdoctoral researcher Gizler, the lead author of the research papers, states: "Inhibiting excessive liver GABA production restored insulin sensitivity within days, and prolonged inhibition of liver transaminase (GABA) led to reduced food intake and subsequent weight loss."
For his part, Rinkewist reiterates that the new findings are just the first step towards practical application, and research is still far from producing a medication at this time. However, he observes: "Nonetheless, the magnitude of the obesity crisis makes these promising results an important first step that we hope will ultimately impact the health of our families, friends, and communities."
