The balance of our blood sugar levels relies on the pancreatic beta cells’ ability to sense glucose and release insulin. When these cells fail to work properly, it can lead to diabetes. Previously, scientists believed that beta cells needed support from other pancreatic hormone-producing cells to function effectively. However, researchers from the University of Geneva (UNIGE) have now shown the opposite: in adult mice that possess only beta cells in their pancreas, the regulation of blood sugar and the sensitivity to insulin is actually superior compared to typical mice. These groundbreaking findings, which hold significant clinical implications, are detailed in the journal Nature Metabolism.
In 2010, a research group led by Pedro Herrera, a professor at the UNIGE Faculty of Medicine’s Department of Genetic Medicine and Development and the Diabetes Centre, discovered an impressive ability of pancreatic cells to adapt their function. When beta cells are lost early, other endocrine cells that usually produce hormones such as glucagon or somatostatin can begin making insulin instead.
”It was previously believed that differentiated adult cells were incapable of regenerating or altering their functions. Stimulating this cellular adaptability could potentially lead to a new diabetes treatment. But what happens if all endocrine pancreatic cells lose their original roles and start producing insulin? That’s what we aimed to explore in our latest study,” explains Pedro Herrera.
Other endocrine cells are not necessary
It was commonly accepted that beta cells require the presence of other hormone-producing cells—those that create alpha, delta, and gamma hormones—in the pancreatic islets to function well. ”To test this, we created mice that could have all non-beta cells in their pancreas selectively removed as they reach adulthood, allowing us to examine how the beta cells handle blood sugar regulation,” states Marta Perez Frances, a researcher in Pedro Herrera’s lab and the main author of this study. ”Surprisingly, our mice managed to maintain effective blood sugar control and were healthier than the control group!”
Even when subjected to a high-fat diet or insulin resistance testing, which is a key indicator of diabetes, these mice demonstrated enhanced insulin sensitivity in all targeted tissues, especially in fat tissue. Why is that? “The body adapts by recruiting hormonal cells from outside the pancreas to counter the loss of glucagon and other pancreatic hormones,” Pedro Herrera notes. ”This clearly illustrates that the non-beta cells within pancreatic islets are not essential for maintaining blood sugar balance.” These findings are unexpected and challenge previous assumptions.
Emerging new therapies
Typically, around 2% of pancreatic cells will switch their roles when insulin is deficient. The next step is to find a molecule that can trigger and enhance this transformation. Another approach may involve differentiating stem cells in a lab to generate new beta cells for transplantation into patients. ”Our findings provide strong evidence that methods targeting insulin-producing cells could be highly effective,” said Pedro Herrera enthusiastically. ”The following stage of our research will focus on establishing the molecular and epigenetic profiles of non-beta cells from both diabetic and non-diabetic individuals, in hopes of discovering the factors that might enable us to induce this conversion in the context of diabetes pathology.”
