miRNAs appear to play an important role in blocking the effect of insulin in obesity, through a mechanism that leads to insulin resistance of the cells, according to scientists at the Max Planck Institute for Neurological Research and the Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD).
Details were published online March 27 in Nature Cell Biology. The paper is titled "Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism.”
The researchers compared normal weight mice with obese mice with type 2 diabetes. They found that that the diseased animals produce more than twice as much miRNA-143 in their livers than the normal ones. Additionally, they observed a low concentration of the protein ORP8 in the obese mice that formed large quantities of miRNA-143.
Under normal circumstances ORP8 stimulates insulin to activate enzyme AKT, reducing the sugar content of the blood. If ORP8 is lacking, insulin is unable to take effect, and the AKT remains inactive.
Researchers are yet to determine why obese mice form more miRNA-143 than their normal weight counterparts. "If we succeed in explaining the signalling paths in the cell that lead to the production of miRNA-143, we will have a starting point for the development of new drugs for the treatment of type 2 diabetes," Dr. Brüning says.