A new method for treating type 2 diabetes

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This year marks the 100th anniversary of the discovery of insulin, a scientific discovery that transformed type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, from a terminal illness into a manageable condition. More recently, researchers believe the liver may hold the key to new preventative treatments for type 2 diabetes.

“We need another discovery”

Today, type 2 diabetes is 24 times more common than type 1 diabetes. Rising rates of obesity and the incidence of type 2 diabetes are correlated and require new approaches, according to researchers at the University of Arizona, who believe the liver may have the key to new treatment innovation.

“All current therapies for type 2 diabetes are primarily aimed at lowering blood sugar. So it treats a symptom, just like treating the flu by lowering the fever, ”said Benjamin Renquist, an associate professor at the Arizona College of Agriculture and Life Sciences.

In two papers recently published in Cell Reports , Renquist, along with researchers at the University of Washington in St. Louis, the University of Pennsylvania and Northwestern University, present a new goal for the treatment of type 2 diabetes. Renquist, whose research lab aims to address obesity-related diseases, has spent the past nine years better understanding the correlation between obesity, fatty liver disease and diabetes, especially how the liver affects insulin sensitivity.

“Obesity is known to be a cause of type 2 diabetes, and we’ve known for a long time that the volume of liver fat increases with obesity,” Renquist said. “As fat grows in the liver, so does the incidence of diabetes.”

This suggested that liver fat could be the cause of type 2 diabetes, but how liver fat could cause the body to become insulin resistant or cause the pancreas to secrete excessive insulin remained a mystery.

Renquist and colleagues focused on fatty liver, measuring the neurotransmitters released from the liver of animals into models of obesity, to better understand how the liver communicates with the brain to influence the metabolic changes observed in obesity and diabetes.

How do liver fats work?

Liver fat has been found to increase the release of the inhibitory neurotransmitter Gamma-aminobutyric acid, or GABA. “We then identified the pathway between the synthesis of GABA and the key enzyme that is responsible for the production of GABA in the liver – GABA transaminase. A natural amino acid, GABA is the main inhibitory neurotransmitter in the central nervous system, which means that it decreases nervous activity, ”says Renquist.

The nerves provide a conduit through which the brain and the rest of the body communicate. This communication is not only from the brain to other tissues, but also from the tissues back to the brain, Renquist also explained.

“When the liver produces GABA, it decreases the activity of nerves that pass from the liver to the brain. Thus, the fatty liver, through the production of GABA, decreases the burning activity towards the brain “, said Renquist. This decrease in trigger is noticed by the central nervous system, which changes the output signals that affect glucose homeostasis.

To determine whether increased hepatic GABA synthesis caused insulin resistance, Renquist Laboratory students Caroline Geisler and Susma Ghimire pharmacologically inhibited hepatic GABA transaminase in animal models of type 2 diabetes.

“Inhibiting excess hepatic GABA production restored insulin sensitivity within days,” said Geisler, now a postdoctoral researcher at the University of Pennsylvania and lead author of the paper. Longer-term inhibition of GABA transaminase has led to decreased food intake and weight loss.

The researchers wanted to ensure that the findings could be applied to humans

Kendra Miller, a research technician at Renquist Laboratory, identified genome variations near GABA transaminase that were associated with type 2 diabetes. Working with researchers at the University of Washington, they showed that in people with insulin resistance, the liver has genes more strongly involved in the production and release of GABA.

The findings are the basis of a clinical study funded by the Arizona Biomedical Research Commission, currently underway at the University of Washington School of Medicine in St. Louis. Louis, along with collaborator Samuel Klein, co-author of the study and professor of medicine and nutritional science at the University of Washington. The study will investigate the use of an FDA-approved and commercially available GABA transaminase inhibitor to improve insulin sensitivity in obese people.

However, this study is the first step, the research is a few years away until it reaches the pharmacies in the neighborhoods. But until then, you have other tools at your fingertips to help you fight obesity. Download now the free Dahna app from the AppStore or Google Play and let the cardiologists and nutritionists guide you correctly and efficiently for a healthy life!

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