A new study has found a link between high blood insulin levels, frequently seen in people with obesity and type 2 diabetes, and pancreatic cancer. The researchers say their findings may lead to new cancer prevention strategies and targeting treatments to slow or prevent the progression of the cancer.
Obesity and type 2 diabetes (T2D) are among the risk factors for pancreatic cancer, and pancreatic ductal adenocarcinoma (PDAC) is one of the most prevalent, aggressive, and lethal pancreatic cancers. However, the mechanisms by which T2D and obesity contribute to PDAC have remained unclear.
Now, a new study by researchers at the University of British Columbia in Canada has shed light on the role that insulin and its receptors play in the development of PDAC.
“Alongside the rapid increase in both obesity and type 2 diabetes, we’re seeing an alarming rise in pancreatic cancer rates, said James Johnson, one of the corresponding authors of the study. “These findings help us understand how this is happening and highlight the importance of keeping insulin levels within a healthy range, which can be accomplished with diet, exercise and, in some cases, medications.”
The pancreas performs exocrine and endocrine functions. Acinar cells (exocrine) synthesize, store, and secrete enzymes into the small intestine that help digest food, whereas beta cells (endocrine) make the hormone insulin, which regulates blood glucose levels. Insulin is thought to bind to its own receptor on the acinar cell, stimulating enzyme secretion.
T2D results from a combination of ineffective and insufficient insulin, leading to insulin resistance and high blood insulin (hyperinsulinemia) as the body produces more of the hormone to bring down high blood glucose levels (hyperglycemia). It’s commonly accepted that in obesity, elevated free fatty acid levels cause insulin resistance, which, because of the resulting hyperglycemia, also leads to hyperinsulinemia.
Using mice models, the researchers examined what was happening in the pancreatic acinar cells when the animals were hyperinsulinemic.
“We found that hyperinsulinemia directly contributes to pancreatic cancer initiation through insulin receptors in acinar cells,” said Anni Zhang, the study’s lead author. “The mechanism involved increased production of digestive enzymes, leading to heightened pancreatic inflammation.”
The researchers propose that this inflammation leads to the development of precancerous cells. Their findings may pave the way for new cancer prevention strategies and therapeutic approaches that target insulin receptors on acinar cells.
“We hope this work will change clinical practice and help advance lifestyle interventions that can lower the risk of pancreatic cancer in the general population,” said Janel Kopp, co-corresponding author. “This research could also pave the way for targeted therapies that modulate insulin receptors to prevent or slow the progression of pancreatic cancer.”
The researchers also say their findings may have implications for other cancers associated with obesity and T2D, where elevated insulin levels may also play a contributing role.
“Colleagues in Toronto have shown similar connections between insulin and breast cancer,” Johnson said. “In the future, we hope to determine whether and how excess insulin might contribute to other types of obesity- and diabetes-driven cancers.”
The study was published in the journal Cell Metabolism.
Source: University of British Columbia
