Beta Cells Function Independently for Glycemic Control

The ability of the pancreatic beta cells to recognize glucose and release insulin to regulate our blood sugar levels is the foundation of our glycemic balance. Diabetes develops when there is a disruption in the balance caused by these cells. Up until now, scientists have accepted that the other hormone-producing cells in the pancreas are necessary for beta cells to perform their intended functions. On the other hand, glycemia management and insulin sensitivity are much better in adult mice whose pancreas consists of just beta cells, as shown by a team from the University of Geneva (UNIGE). Read about these findings, which provide significant clinical opportunities, in the journal Nature Metabolism.

The amazing ability of pancreatic cells to change function was discovered in 2010 by a team led by Pedro Herrera, a professor at the UNIGE Faculty of Medicine in the Department of Genetic Medicine and Development and the Diabetes Center. The endocrine cells that are typically in charge of creating other hormones like glucagon or somatostatin may begin producing insulin if beta cells die too soon.

“Until now, it was thought that the differentiated adult cells of an organism could not regenerate and reorientate themselves functionally. 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.” – Pedro Herrera, Professor in the Department of Genetic Medicine and Development and in the Diabetes Centre at the UNIGE Faculty of Medicine

Non-beta cells don’t matter
It was acknowledged that the other hormone-producing cells—gamma, delta, and alpha cells—grouped in islets within the pancreas, were necessary for beta cells to operate properly. First author of this work Marta Perez Frances, a researcher in Pedro Herrera’s lab, says, “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 glycaemia.” “Our mice were surprisingly even healthier than the control mice, and they were perfectly capable of managing their blood sugar levels!”

These animals demonstrated enhanced sensitivity to insulin in all target tissues, including adipose tissue, even when given a high-fat diet or tested for insulin resistance, one of the primary indicators of diabetes. Why? Pedro Herrera says, “To deal with the abrupt reduction in glucagon and other pancreatic hormones, the body goes through an adaptation process in which it recruits other hormonal cells from outside the pancreas.” However, this demonstrates unequivocally that the pancreatic islets’ non-beta cells are not necessary for preserving glycemic homeostasis. These unexpected findings cast doubt on the previously held belief.

Novel therapeutics in development
Naturally, in the event of insulin deprivation, about 2% of pancreatic cells alter their function. Finding a chemical that can trigger and enhance this conversion is now the task. A different tactic would be to create new beta cells in vitro using stem cells and then transplant them into the patients.

”Our results are proof that strategies focusing on insulin cells could really pay off,” enthuses Pedro 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.”

For more information: Regulated and adaptive in vivo insulin secretion from islets only containing β-cells, Nature Metabolism, https://doi.org/10.1038/s42255-024-01114-8