New research that subverts diabetes! This hormone actually dominates insulin resistance and becomes a key target for treatment?

Diabetes, especially type 2 diabetes, has become a global health challenge, affecting the quality of life of hundreds of millions of people. Previous studies have mainly focused on the phenomenon of insulin resistance in metabolic target cells such as skeletal muscle, fat and liver, but these studies have not fully revealed the origin and mechanism of insulin resistance.

In order to explore this issue in depth, a research team from the Max Planck Institute for Heart and Lung Research in Germany decided to take a different approach. Their research not only focused on traditional metabolic target cells, but also turned their attention to a key molecule that mediates insulin resistance, adrenomedullin. The study found that adrenomedullin (a peptide hormone whose concentration increases in obesity) can inhibit insulin signaling in human and mouse endothelial cells. In addition to exploring the underlying principles of this mechanism, the study also confirmed through mouse model experiments that adrenomedullin receptor antagonists (a drug that can prevent adrenomedullin from working) have a beneficial effect on improving insulin sensitivity, pointing out potential directions for future treatment strategies.

Research Methods and Process

In order to further explore the potential mechanism of insulin resistance, the researchers conducted a comprehensive and systematic screening and analysis of insulin signaling-related receptors in endothelial cells. In the process, they identified the CALCRL receptor (a cell surface receptor involved in a variety of physiological and pathological processes) that is closely linked to changes in insulin receptor activity. This discovery laid an important foundation for subsequent research.

In order to verify the actual role of CALCRL receptors, the researchers designed an animal model experiment : on the one hand, they knocked out the CALCRL receptors of mice and observed the glucose metabolism response of these mice under the challenge of a high-calorie diet; on the other hand, they injected adrenomedullin into healthy mice to simulate the hormonal environment in an obese state, and then evaluated the changes in glucose tolerance and insulin sensitivity of these mice. In addition, the researchers also used adrenomedullin receptor antagonists to intervene in obese type 2 diabetic mice in order to observe the potential effects of the antagonist in improving glucose tolerance and insulin sensitivity.

Research findings and prospects

1. The role of adrenomedullin: Studies have found that adrenomedullin, a hormone mainly released by adipose tissue, interferes with insulin signaling in endothelial cells, leading to insulin resistance in endothelial cells and even the whole body. Simply put, this hormone makes the body's response to insulin slow.

2. Insulin resistance in blood vessels: Insulin needs to be transported through the blood and pass through the endothelial cells to reach the target tissue. If there is a problem with this transportation process, the effect of insulin will be greatly reduced. Studies have confirmed that in type 2 diabetes caused by obesity, there is indeed insulin resistance in the endothelial cells of the blood vessels, which means that it is difficult for insulin to reach and work smoothly.

3. Experiments have confirmed that mice whose CALCRL receptors have been removed can maintain normal glucose metabolism even in an obese state. After healthy mice were injected with adrenomedullin, their glucose tolerance and insulin sensitivity decreased significantly. In addition, the study found that the use of adrenomedullin receptor antagonists can effectively improve insulin resistance caused by obesity. These experimental results further confirm the key role of adrenomedullin in insulin resistance and provide a new direction for the future treatment of diabetes.

4. Research prospects: This study provides a new perspective for us to understand the underlying mechanism of type 2 diabetes. Adrenomedullin, as a key molecule mediating insulin resistance, is expected to become a new target for the treatment of type 2 diabetes. In the future, drug development targeting adrenomedullin and its receptors may bring new treatment options for diabetic patients.

How to prevent diabetes

1. Healthy diet: Maintain a balanced diet, limit the intake of high-calorie, high-sugar, and high-fat foods, and increase the proportion of vegetables, fruits, and whole grains.

2. Exercise moderately to control your weight: Regular moderate-intensity aerobic exercise, such as brisk walking, swimming, cycling, etc., can help improve insulin sensitivity; maintain a healthy weight and avoid abdominal obesity.

3. Regular check-ups: Perform regular blood sugar tests to detect and treat prediabetes in a timely manner.

4. Quit smoking and limit alcohol consumption: Smoking and excessive drinking are both risk factors for diabetes and should be avoided as much as possible.

5. Reduce stress: Long-term mental stress can also affect blood sugar levels. Learning to relax and reduce stress is crucial to preventing diabetes.

References:

HaaglimCho, et al.Endothelial insulin resistance induced by adrenomedullin mediatesobesity-associated diabetes.Science387,674-682(2025).DOI:10.1126/science.adr4731