According to a study published in Signal Transduction and Targeted Therapy, researchers led by Prof. LIU Qingsong from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences reported an approach to the treatment of diabetes by developing a novel dual regulatory molecule, IHMT-MST1-39, which affects both MST1 and AMPK, two proteins associated with diabetes.

Diabetes is a chronic disease that affects millions of people worldwide. It occurs when the body is unable to produce or use insulin properly, resulting in high levels of glucose in the blood. The death of insulin-producing pancreatic beta cells is a key factor in the development of type I diabetes, while type II diabetes is characterized by metabolic dysfunction.

In this study, the researchers focused on two key proteins: MST1 and AMPK and proposed that inhibiting MST1 kinase plays a role in pancreatic β-cell apoptosis and insulin secretion, while activating AMPK helps coordinate the cellular response to energy stress, could be an effective strategy for diabetes treatment.

Using a rational drug design strategy, the team developed IHMT-MST1-39, a potent and selective MST1 kinase inhibitor. In laboratory tests, the compound was shown to improve pancreatic β-cell survival and function, and in vivo studies showed that it was effective in reducing fasting blood glucose, food and water intake, and lowering glycosylated hemoglobin levels.

When combined with metformin, the first-line clinical treatment for diabetes, the glucose-lowering effect was even more significant. Further research showed that IHMT-MST1-39 in combination with metformin also significantly increased AMPK activity in the liver, leading to improved glucose tolerance and insulin resistance.

This study provides new insights into the potential role of simultaneous modulation of MST1 and AMPK activities in the treatment of diabetes.

IHMT-MST1-39's Effect on Fasting Blood Glucose Levels in Type I Diabetic Mouse Models. (Image by WANG Junjie)