Understanding Why Insulin-Producing Cells Fail in People with Type 2 Diabetes
Preventing Diabetes
Jin Li, PhD, University of Michigan Medical School Published inNature Metabolism, July 2025
Diabetes is a complex disease, but at its center are the insulin-producing beta cells in the pancreas. In people with type 2 diabetes, beta cells die off—a process that, combined with insulin resistance, leads to chronic high blood glucose (blood sugar) levels.
Dr. Li, a recipient of an American Diabetes Association® (ADA) Postdoctoral Fellowship Award, has shed light on how this happens. “Once someone is diagnosed with type 2 diabetes, at least 30% of their beta cells are already completely gone,” she explained. “If we can identify the pathways that damage beta cells, we may be able to create new diabetes treatments that are more effective than the drugs we use today.”
Scientists already knew that misfolded proteins are an early trigger of beta cell failure in type 2 diabetes, but most research focused on a part of the cell called the endoplasmic reticulum. Dr. Li’s research was the first to reveal that most protein misfolding instead happens in the mitochondria, often referred to as the cell’s “powerhouse.”
Dr. Li and her colleagues also found unusually low levels of a protein called LONP1 in pancreatic cells from people with type 2 diabetes, which turned out to be the key to keeping beta cell mitochondria healthy. Removing LONP1 in mice caused their beta cells to die, resulting in less insulin and elevated blood glucose. When the researchers boosted LONP1, it prevented mitochondrial protein misfolding, improving beta cells’ survival.
This insight into how type 2 diabetes develops at the cellular level suggests a potential new way to prevent or delay the disease. A treatment that enhances LONP1 could help protect or restore insulin production to keep a person’s blood glucose in a healthier range.
Dr. Li’s interest in diabetes research is both personal and professional. Diabetes is a major risk factor for heart disease, her previous area of focus. When several of her family members were diagnosed with type 2 diabetes, she grew even more curious about its causes.
She credits the ADA grant with supporting her career path and connecting her to the wider diabetes research community. “I appreciate getting financial support from the ADA to expand my research … and collaborating with other researchers has been super beneficial,” she said.
Next, Dr. Li plans to explore why LONP1 levels drop and whether other mitochondrial proteins play a similar role in type 2 diabetes. She hopes to one day open a research lab focused on translating discoveries like hers into diabetes treatments.
She added: “I love diabetes research because there are still so many unsolved things to figure out.”