Researchers at the Tohoku University Medical School have revealed a key primary step on the ERK hepatic route that leads to increased insulin production. While their previous work focused on aspects of the liver signaling route to the pancreas, this current study shows another previous step that begins in the colon when it is inflammatory – activated by obesity. The present study revealed a new role played by the gastrointestinal tract in regulating glucose homeostasis.
Insulin is a hormone produced by β-cells in the pancreas. You can think of insulin as a key that unlocks cells to let glucose enter the blood so that it can be used as energy. However, people with obesity can become insulin -resistant, which forces the pancreas to secrete more insulin to try to continue. This is through a neuronal signal relay between the organs derived from the ERK hepatic route. Due to the close relationship between obesity and the appearance of diabetes, understanding this path in depth could help develop new ways to deal with or prevent this situation.
The purpose of this study was to determine how obesity specifically activates this cataract. We thought it had to do with inflammation in the colon, since pre-inflammatory agents can play a stimulant role on the ERK hepatic road. “
Junta Imai, tohoku University
The researchers developed a thorough series of experiments to determine whether the inflammation of the colon due to obesity could affect the ERK liver pathway. First, the research team analyzed mice without obesity that had been given a drug to cause inflammation in the colon. As a result, they found that simply causing inflammation in the colon activates the ERK Street in the liver, stimulates the neuronal relay route and increases the number of beta-cells even in mice without obesity. Then, analyzing the cologne of the mice that caused obesity from a high calorie diet, it was found that the inflammation of the colon, along with the activation of the ERK hepatic route and the increased β-cells, in these obese mice.
“An exciting finding was when we tried to deal with obese mice with colon inflammation by reducing their inflammation. It actually stopped the ERK trail to the liver to activate,” Imai explains. “Despite the fact that the mouse was still obese, the targeting of colon inflammation was exactly what it needed to change ERK Street.”
This research reveals an missing link on the trail, specifying that the liver feels the condition of obesity through the inflammation of the colon and the inflammation of the colon serves as the first trigger of beta-cell proliferation during obesity. These achievements will lead to developments in understanding the mechanism behind the proliferation of beta-cells in order to maintain normal blood glucose levels. In addition, it is expected that this research can help in the progress of developing treatments and prevention methods for diabetes.
These findings were published in JCI Insight On May 8, 2025.
This research was supported by the Japanese Science Promotion Society (JSPS) Kakenhi Grant-in-Aid for scientific research (23K24383, 22K19303, 20H05694). The Japanese Science and Technology Service (JST), Moonshot’s R&D (JPMJMS2023). and the Japanese Medical Research and Development Service (Amed), Amed-Prime (21GM6210002H0004).
Source:
Magazine report:
Kubo, H., et al. (2025). The inflammation of the university causes the proliferation of B cells in the development of obesity through a mechanism between the liver to the-Pancreas. JCI Insight. doi.org/10.1172/jci.insight.183864.
