The beta cells of the pancreas don’t need the assistance of other pancreatic cells to produce insulin, according to new research. The findings are not only a potential game-changer for diabetics, but they challenge a long-held assumption about how the body produces insulin.
Healthy beta cells in the islets of the pancreas produce insulin in response to a rise in blood glucose after eating. However, if the beta cells aren’t functioning properly or have been destroyed, producing little or no insulin, diabetes develops.
It’s always been accepted that beta cells don’t act alone, that they act together with other hormone-producing pancreatic cells – alpha, delta, and gamma cells – to maintain blood glucose levels. However, a new study by researchers at the University of Geneva (UNIGE) in Switzerland has challenged the prevailing belief.
“Until now, it was thought that the differentiated adult cells of an organism could not regenerate and reorientate themselves functionally,” said Pedro Herrera, a professor at the Department of Genetic Medicine and Development at UNIGE and the study’s co-corresponding author. “Pharmacologically triggering this cellular plasticity could, therefore, form the basis of an entirely new therapy for diabetes. But what happens if all the cells of the endocrine pancreas abandon their original function to start producing insulin? It is what we wanted to find out in our new study.”
In 2010, Herrera and his researchers discovered that if beta cells die prematurely, the pancreatic cells responsible for producing other hormones such as glucagon, which counteracts insulin’s effects to raise blood glucose and is produced by alpha cells, or somatostatin, produced by delta cells and a powerful inhibitor of insulin secretion, could start producing insulin. In the current study, they looked at whether non-beta cells were even necessary for insulin production.
“To verify this, we produced mice in which, when they reach adulthood, all the non-beta cells in the pancreas can be selectively eliminated to observe how the beta cells manage to regulate glycemia [blood glucose],” said Marta Perez Frances, a researcher in Herrera’s lab and the lead author of the study. “Surprisingly, not only were our mice perfectly capable of managing their blood sugar levels effectively, but they were even healthier than the control mice!”
They found that the near-total loss of non-beta cells did not affect the mice’s feeding behavior, body weight, or blood glucose control, even when they were fed a high-fat diet. In fact, when they examined slices of pancreas and isolated clusters of cells composed exclusively of beta cells, the researchers found that they exhibited insulin secretion dynamics similar to regular pancreatic islets, which contain alpha, beta, delta and gamma cells.
The beta-cell-only mice showed consistent improvement in insulin sensitivity and glucose tolerance, lacking in human diabetics, in all the target tissues, particularly the fatty or adipose tissue.
“There is an adaptation process in which the body recruits other hormonal cells from outside the pancreas to cope with the sudden reduction in glucagon and other pancreatic hormones,” Herrera said. “But this clearly shows that non-beta cells of the pancreatic islets are not essential for maintaining the glycemic balance.”
While it’s still early days, the study’s findings could be a game-changer for diabetics. It may be possible, for example, to produce new beta cells from stem cells before transplanting them into patients.
“Our results are proof that strategies focusing on insulin cells could really pay off,” said Herrera. “The next stage of our work will therefore involve establishing the molecular and epigenetic profile of non-beta cells from diabetic and non-diabetic individuals in the hope of identifying the elements which could make it possible to induce the conversion of these cells in the pathological context of diabetes.”
The study was published in the journal Nature Metabolism.
Source: UNIGE
