How is insulin resistance caused?

A new work in mice reveals changes in the pattern of microRNAs that cause glucose intolerance and insulin resistance. The study, published in the journal PNAS, explains the role of these molecules, related to obesity, in the onset of diabetes.

Researchers at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Biomedical Network Research Center for Diabetes and Associated Metabolic Diseases (CIBERDEM) have found that changes in the microRNA content of exomes constitute a vehicle by which obesity causes insulin resistance in mice.

These changes in the pattern of the microRNAs cause glucose intolerance and insulin resistance. The study, published in the journal ‘PNAS’, provides a new therapeutic target for the treatment of metabolic syndrome.

The work has been coordinated by the head of the IDIBAPS Diabetes Prevention and Pathogenesis team and group leader of CIBERDEM, Dr. Anna Novials, and the first author of the same is a predoctoral researcher of the group, Carlos Castaño. For its part, the last author of the work is also researcher Marcelina Párrizas.

MicroRNAs are small molecules that have the ability to regulate the expression of genes and can secrete almost all types of cells in the body inside vesicles called exosomes. They contain proteins, lipids or RNA molecules in the metabolic syndrome.

Changes in the profile of circulating microRNAs in the blood are associated with several diseases, including metabolic diseases. These molecules can be used as biomarkers to improve the diagnosis of diseases and monitor the response to treatments.

Obesity is defined as an increase in body fat composition. This increase translates into an increase in weight and although not every increase in body weight is due to an increase in adipose tissue, in medical practice the concept of obesity is related to body weight. Obesity should be understood as a chronic disease, similar to diabetes mellitus or hypertension.

Obesity is a chronic, complex and multifactorial disease that usually begins in childhood and adolescence, and that has its origin in a genetic and environmental interaction, being more important the environmental or behavioral part, which is established by an imbalance between intake and energy expenditure.

Obesity is often related to metabolic diseases. Type 2 diabetes is one of the most common metabolic diseases and it is estimated that it will affect a third of the population in 2050. This type of diabetes is associated with overweight and sedentary lifestyle, and is one of the main causes of insulin resistance. .

In the study, researchers have observed the role of microRNAs with a diabetic mouse model that simulates the metabolic syndrome. Through a diet rich in fats, animals become intolerant to glucose, as a pre-diabetic state, have fatty liver and disorder in lipid metabolism.

Also in healthy mice

The scientists obtained a panel through a bioinformatic analysis and the results show that obesity changes the profile of microRNAs in plasma exosomes in mice.

Furthermore, if healthy mice are treated with the exomes isolated from obese mice, glucose intolerance and insulin resistance are caused. The researchers managed to reproduce in the laboratory the pattern of microRNAs associated with obesity and saw that the transfer to healthy mice also caused them the same metabolic syndrome.

“In this study we have explained the role played by exosomes and certain microRNAs related to obesity in the onset and development of insulin resistance and diabetes. Now, the future is to block these molecules so that the disease does not appear, “said Dr. Novials.

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