The relationship between obesity and diabetes has long been a subject of scientific interest. Researchers at Tohoku University Graduate School of Medicine have made a groundbreaking discovery that sheds light on the missing link between these two conditions. Their study reveals that colonic inflammation, triggered by obesity, plays a crucial role in regulating glucose homeostasis through the hepatic ERK pathway.

Insulin is a hormone produced by β-cells in the pancreas that unlocks cells to let glucose enter from the blood. However, individuals with obesity often become insulin-resistant, causing their pancreas to secrete more insulin to try and keep up. This study shows that inflammation in the colon, triggered by obesity, activates the ERK pathway in the liver, which stimulates the neuronal relay pathway and increases β-cell production.

The researchers conducted a series of experiments on mice to determine if colonic inflammation due to obesity could impact the hepatic ERK pathway. They found that causing inflammation in the colon activated the ERK pathway in the liver, stimulated the neuronal relay pathway, and increased β-cells even in mice without obesity. By analyzing colons of mice with induced obesity, they also found that colonic inflammation had occurred along with both hepatic ERK pathway activation and increased β-cells.

Moreover, when the researchers treated obese mice with colon inflammation by lowering their inflammation, it actually stopped the ERK pathway in the liver from activating. This exciting finding suggests that targeting colon inflammation could be a potential way to prevent or treat diabetes.

This research has significant implications for understanding the mechanism behind β-cell proliferation and maintaining normal blood glucose levels. It is anticipated that these findings will lead to advancements in developing treatments and prevention methods for diabetes, ultimately improving the lives of millions of people worldwide.

The study was published in JCI Insight on May 8, 2025, and was supported by various grants from the Japan Society of the Promotion of Science (JSPS), Japan Science and Technology Agency (JST), and Japan Agency for Medical Research and Development (AMED).

The article presents a promising strategy to prevent or slow the progression of Type 1 diabetes by targeting an inflammation-related protein known to drive the disease. Researchers have found that applying a molecular method to block inflammation signaling through the tyrosine kinase 2 (TYK2) protein reduces harmful inflammation in the pancreas, protecting insulin-producing beta cells and calming the immune system’s attack on those cells.

Type 1 diabetes is a lifelong condition where the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. This leads to high blood sugar levels, requiring ongoing insulin therapy and careful monitoring to avoid severe health complications.

The study, co-led by Indiana University School of Medicine researchers, presents a potential new strategy using a medication that inhibits TYK2, which is already approved for the treatment of psoriasis, an autoimmune condition causing skin inflammation. This finding is exciting because there is already a drug on the market that can do this for psoriasis, which could help move toward testing it for Type 1 diabetes more quickly.

Past genetic studies have shown that people with naturally lower TYK2 activity are less likely to develop Type 1 diabetes, further supporting the group’s approach for future treatments using this TYK2 inhibitor approach.

The researchers hope their findings will support future clinical trials to safely assess the efficacy of a new drug or drug combination in humans. They emphasize the importance of initiating translational studies to evaluate the impact of TYK2 inhibition alone or in combination with other already approved drugs in individuals at-risk or with recent onset Type 1 diabetes.

The study’s lead author, Farooq Syed, PhD, notes that their preclinical models suggest that the treatment might work in people as well. The next step is to initiate translational studies to evaluate the impact of TYK2 inhibition alone or in combination with other already approved drugs in individuals at-risk or with recent onset Type 1 diabetes.

The research team hopes to support future clinical trials to safely assess the efficacy of a new drug or drug combination in humans, offering hope for a potential treatment approach for Type 1 diabetes.

The discovery of how impaired mitochondrial dynamics and quality control mechanisms contribute to insulin resistance related to type 2 diabetes has shed new light on the complex interplay between mitochondria and metabolic health. Researchers at Pennington Biomedical Research Center have made groundbreaking findings, published in the Journal of Cachexia, Sarcopenia and Muscle, that reveal critical insights into how certain enzymes regulate mitochondrial dynamics within skeletal muscle.

The study, led by Dr. John Kirwan, Executive Director of Pennington Biomedical, focused on the significance of deubiquitinating enzymes (DUBs) in maintaining mitochondrial quality control. The research team found that impaired mitophagy, the process by which cells remove damaged mitochondria, can lead to mitochondrial fragmentation as a compensatory mechanism. This adaptation allows skeletal muscle cells to sustain function despite metabolic challenges.

In individuals with type 2 diabetes, a specific protein called dynamin-related protein 1 (DRP1) is overactive, causing an imbalance in mitochondrial dynamics. Furthermore, the team discovered that certain DUBs interfere with mitophagy, making it more difficult for muscles to use insulin properly. This intricate interplay between mitochondria and insulin sensitivity has significant implications for our understanding of type 2 diabetes.

The research findings advance the knowledge on how impaired mitochondrial dynamics and quality control contribute to skeletal muscle insulin resistance and the manifestation of type 2 diabetes. Moreover, they provide crucial evidence that DUB antagonists may play a vital role in preventing or treating type 2 diabetes.

“Our study highlights the complex relationship between mitochondria and insulin,” said Dr. Kirwan. “We are excited about the potential for future interventions aimed at improving metabolic health, particularly in the context of type 2 diabetes.”