Type 2 diabetes is characterized by high blood sugar levels caused by insulin resistance (a hormone that helps glucose enter cells, where it can be used for energy or stored for future use). Insulin resistance occurs when cells in the body do not respond well to insulin and therefore do not remove glucose from the blood.
In type 2 diabetes, insulin resistance also increases the body’s production of insulin, which can lead to increased appetite, high blood pressure and weight gain. Previous research has shown that type 2 diabetes is strongly linked to obesity and fatty liver disease. According to the US Centers for Disease Control and Prevention (CDC), 89% of people with diabetes are overweight.
Obesity, type 2 diabetes and liver medicines
While scientists have long suspected that excess liver fat could cause type 2 diabetes, the exact manner has remained a mystery. In this context, researchers from several American universities have conducted some studies to separate the basic mechanisms that link fatty liver disease to glucose homeostasis (the balance between insulin and blood glucose).
The scientists found that insulin sensitivity can be restored within days of reducing excessive production of the neurotransmitter GABA in the liver and that long-term treatment can lead to decreased appetite and weight loss. Neurotransmitters are sent between the nerves to allow the brain and various parts of the body to communicate. GABA is an inhibitory neurotransmitter, which means that the signaling in the nervous system decreases.
From the study of mice, researchers first found that obesity-induced fatty liver disease increases GABA production in the liver. They then found that the increased GABA signal from the liver affects glucose homeostasis. Because previous research has found that an enzyme called GABA transaminase (GABA-T) is essential for the production of GABA in the liver, the team suspected that targeting GABA-T to produce less GABA in the liver may reduce insulin resistance and treat diabetes. type 2.
To test their hypothesis, the researchers first treated mouse models of type 2 diabetes with drugs that inhibit GABA-T activity. These drugs are known as ethanolamine-O-sulfate (EOS) and vigabatrine.
The team’s second means of testing its hypothesis involved a genetic treatment known as antisense oligonucleotide (ASO). This works by binding small pieces of DNA or RNA to RNA molecules to stop the production of certain proteins. In this case, ASO worked by disabling GABA-T expression in the liver.
Both treatment methods reduced GABA-T activity and improved insulin sensitivity in a few days. Mice given ASO and EOS also lost 20% of their body weight 7 weeks after starting treatment.
The researchers then examined liver samples taken from 19 obese people during bariatric surgery procedures. Analyzing gene expression in liver tissue, they found that participants with insulin resistance had high levels of expression for genes related to GABA production and activity.
To explain the results, the researchers say that excess fat in the liver increases the release of GABA, which then suppresses the triggering of the related vagal hepatic nerve, a line of communication between the liver and the brain. Suppressing this nerve with GABA increases food intake and weight gain, which increases insulin resistance. Allowing this nerve to start normally has the opposite effect of reducing food intake, weight gain and insulin resistance.
The researchers also tested GABA-T inhibitory methods on weak mice. Because these mice already had low levels of GABA in the liver, the drugs had little or no effect on their insulin levels, blood sugar and body mass.
The researchers concluded that targeting GABA production in the liver can improve glucose homeostasis and also reduce food intake and body mass – exclusively among obese people.
All current therapies for type 2 diabetes are primarily aimed at lowering blood sugar, scientists say, so in other words, treating a symptom, so more advanced therapies are needed. A new pharmacological target is only the first step in implementation, but a drug will arrive in pharmacies after several years.
Although these findings will not change treatment options in the short term, the study authors conclude, they offer scientists a new way to develop new treatments, such as GABA inhibitors, which could in the future help reduce the release of GABA in the liver, which could provide a new way to manage diseases by people with type 2 diabetes.
Treating obesity also helps with type 2 diabetes
Weight loss is an important goal for overweight or obese people, especially for those with type 2 diabetes. Moderate and sustained weight loss (about 5-10% of body weight) can improve the action of insulin, can reduce glucose levels. at rest and decreases the need for medication for diabetes.
A healthy eating program, avoiding sugar and ultra-processed foods (sausages, margarine, pastries, etc.) and regular exercise can successfully treat obesity, but in some cases, surgery may be needed.
Healthy eating means basing meals on the simplest and most natural ingredients (vegetables, fruits, fish, lean meat, moderate amounts of crude oil, nuts, wholemeal bread). Exercises can be done according to preferences and depending on the general health of the person. You can do gymnastics at home or at the gym, you can go cycling or you can take daily walks in the park or hiking in the mountains.
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