A new study by researchers at the University of British Columbia School of Medicine reveals a direct link between high insulin levels, common among patients with obesity and type 2 diabetes, and pancreatic cancer.
The study, published in Cell Metabolism , provides the first detailed explanation of why people with obesity and type 2 diabetes have a higher risk of pancreatic cancer. Research shows that excessive insulin levels overstimulate pancreatic acinar cells, which produce digestive juices. This overstimulation leads to inflammation that turns these cells into precancerous cells.
"Along with the rapid rise in obesity and type 2 diabetes, we are seeing an alarming increase in pancreatic cancer rates," said co-senior author Dr. James Johnson, professor in the department of cellular and physiological sciences and chair interim at the UBC Life Sciences Institute. "These findings help us understand how this happens and highlight the importance of keeping insulin levels within a healthy range, which can be achieved with diet, exercise and, in some cases, medications."
The study focused on pancreatic ductal adenocarcinoma (PDAC), the most prevalent and highly aggressive pancreatic cancer, with a five-year survival rate of less than 10 percent. The incidence of pancreatic cancer is increasing. By 2030, PDAC is expected to become the second leading cause of cancer-related deaths.
Although obesity and type 2 diabetes had previously been established as risk factors for pancreatic cancer, the exact mechanisms by which this occurred were still unclear. This new study sheds light on the role of insulin and its receptors in this process.
"We found that hyperinsulinemia directly contributes to the onset of pancreatic cancer through insulin receptors on acinar cells," said Dr. Anni Zhang, first author of the study who recently graduated with her PhD from UBC. "The mechanism involves increased production of digestive enzymes, leading to increased pancreatic inflammation."
While insulin is widely recognized for its role in regulating blood sugar levels, the study highlights its importance in pancreatic acinar cells. The findings show that insulin supports the physiological function of these cells by producing digestive enzymes that break down high-fat foods, but at high levels, its increased action can inadvertently promote pancreatic inflammation and the development of precancerous cells.
The findings may pave the way for new cancer prevention strategies and even therapeutic approaches targeting insulin receptors in acinar cells.
"We hope that this work will change clinical practice and help advance lifestyle interventions that can reduce the risk of pancreatic cancer in the general population," said co-senior author Dr. Janel Kopp, an assistant professor at the department of cellular and physiological sciences at UBC. "This research could also pave the way for targeted therapies that modulate insulin receptors to prevent or slow the progression of pancreatic cancer."
In collaboration with researchers at Cancer and Pancreas Center BC, the team has initiated a clinical trial to help patients diagnosed with PDAC control their blood sugar and circulating insulin levels with the help of an endocrinologist.
The researchers say the findings may have implications for other cancers associated with obesity and type 2 diabetes, where elevated insulin levels may also play a contributing role in the onset of the disease.
"Colleagues in Toronto have shown similar connections between insulin and breast cancer," Dr. Johnson said. "In the future, we hope to determine if and how excess insulin might contribute to other types of cancers caused by obesity and diabetes."
