A team of researchers at the Faculty of Medicine of the University of Tohoku has identified a key step in the ERK liver signaling route that stimulates insulin production. Although previous studies of the group had already analyzed how the liver sends signals to the pancreas, this new work goes one step back in the chain: it reveals that It all starts in the colon when it becomes inflamed as a consequence of obesity. This finding, published in JCI Insightunderlines the still little explored paper of the gastrointestinal tract in the regulation of glucose in the body.
Insulin, produced by the β cells of the pancreas, acts as a key that allows glucose entry into cells for use as a source of energy. In people with obesity, insulin resistance usually develops, which forces pancreas to increase its production to compensate.
This process is promoted by neuronal signals between organs that are activated through the liver road Erk. Given the narrow link between obesity and diabetes, understand this signaling route in depth opens new possibilities to effectively prevent this disease.
How the inflammation of the colon influences
In conditions such as obesity, where there is insulin resistancethe β cells of the pancreas increase their number and insulin production to maintain stable glucose levels, thus preventing the development of diabetes. This adaptation has been attributed to humoral factors such as glucose, insulin and Serpin B1 protein. However, neuronal signals also participate, especially through the vagus nerve.
It has been shown that ERK road activation in the liver significantly promotes the proliferation of β cells. This process is produced by signals that travel from the liver to the central nervous system through the splanchnic nerves and from there to the pancreas by the vague nerves.
-Studies in murine models have shown that block this interorganic route interrupts the expansion of β cells induced by obesity. The stimulation of the vague pancreatic and the Molecular pathway are also involved in this process. However, this specific neuronal network is still unknown through the ERK liver path.
To check if the inflammation of the colon caused by obesity influences ERK liver activationthe researchers designed a series of exhaustive experiments. In a first phase, they administered a drug that induced colonic inflammation to non -obese mice. The results were revealing: even without obesity, this inflammation was enough to activate the ERK liver pathway, trigger the neuronal signage and increase the number of pancreatic β cells.
Next, the team analyzed mice induced by a calorie diet. In these animals the presence of inflammation in the colon was confirmed, as well as the Erk Via activation in the liver and an increase in β cellswhich reinforces the connection between intestinal inflammation, interorganic signage and insulin regulation.
This study provides a key piece that was missing in the Comprehension of the signaling route: demonstrates that the liver detects the state of obesity through inflammation in the colon, which acts as the initial trigger for the proliferation of β cells during the development of obesity.
These findings open new perspectives on mechanisms that regulate the expansion of these cells to maintain adequate blood glucose levels. In addition, they could pave the way to new therapeutic and preventive strategies against diabetes.
