High-intensity exercise, calorie restriction reduces nerve damage in prediabetic mice, UMich study finds

Researchers from the University of Michigan found that high-intensity exercise and calorie restriction may reduce peripheral nerve damage in prediabetic mice, according to a study published by U-M researchers in November. Published in the journal Diabetes, the research has potential applications in addressing peripheral neuropathy, a complication of diabetes, prediabetes and obesity. 

Peripheral nerves carry messages between the brain and body in response to the environment. Diabetes, prediabetes and obesity can lead to nerve damage, resulting in peripheral neuropathy, a condition that can be painful and debilitating. This condition affects one’s ability to control sensations or movements, leading to weakness, cramps and loss of balance, among other symptoms. 

Previous studies have shown that PN can be improved by diet and exercise. LSA senior Chloe Kiriluk, neurology lab research assistant, said in an interview with The Michigan Daily that the team was motivated to investigate the relative efficiency of types of exercise and diet because prior research was unclear on which were the most efficient. 

“There aren’t specific guidelines as to what types of interventions, like the length of exercise or type of diet, are most beneficial in regards to diabetic peripheral neuropathy,” Kiriluk said.

To investigate this issue, scientists studied how diet and exercise affect health in mice being fed a high-fat diet. One group ate 40% fewer calories for caloric restriction (CR) while another did high-intensity interval training (HIIT). A third group combined both caloric restriction and HIIT. After 12 weeks, the researchers checked the mice’s metabolic health, examined their tissues, and looked for signs of nerve damage. First author Stephanie Eid, research assistant professor of neurology, explained the results in an interview with The Daily. 

“Looking at the interventions, we found that caloric restriction plus or minus exercise improved overall metabolic health,” Eid said. “So they reduced body weight, they reduced fat mass, they increased muscle mass and they improved glucose tolerance. On the other hand, exercise alone was not able to restore much of these parameters.”

Though exercise alone did not improve metabolism, it improved nerve function similarly to CR and CR-HIIT, suggesting that nerve function recovery can occur independently of weight loss or glycemic control improvements. According to Eid, the results show that all the treatments are beneficial in addressing neuropathy, even though they have different effects. 

Eid said while these findings provide valuable information, CR and HIIT may not be a viable option for everyone seeking to improve PN. Many patients with PN also have associated diseases like heart failure or autonomic neuropathy that prevent them from engaging in these lifestyle interventions. To solve this issue, researchers looked to Schwann cells for alternative therapies. 

Damaged Schwann cells can lose their proper function because of conditions like diabetes or obesity, contributing to nerve injury. The study found that activating AMPK, an enzyme that regulates cellular energy homeostasis and metabolism, could restore their function and protect nerve health. Researchers exposed Schwann cells to palmitate, a fatty acid common in high-fat or obese conditions, which caused the cells to develop insulin resistance. This impaired their ability to respond to insulin, a key process for normal cell signaling. However, treating the cells with the drug metformin to activate the AMPK increased insulin sensitivity, restoring normal insulin signaling and improving function, which could help protect nerve tissue.

Senior author Eva Feldman said this research is important because it could impact future treatments for PN, whether through diet and exercise, or Schwann cell therapies.

“By improving our understanding of how diet, exercise and cellular mechanisms like AMPK activation can influence nerve health, this research brings us closer to effective, multifaceted treatments for diabetic peripheral neuropathy that can significantly enhance patient quality of life,” Feldman said.

According to Eid, this research is a positive step forward in treating neuropathy, emphasizing the potential of simple solutions like a balanced diet or exercise to address this complex condition.

“It’s nice to see that we’re getting somewhere,” Eid said. “It’s nice to see that we’re making a difference. For the longest time, neuropathy has been kind of an abandoned disease. People have given up on it because it’s so difficult and multi-factorial. But there’s still hope. And it might be easy. It might be something as simple as having a balanced diet.” 

Daily News Contributor Alaine Hanson can be reached at alaineh@umich.edu.

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