A team from the University of Geneva, Switzerland, has revealed that the cells that produce insulin (beta cells) alone can regulate blood sugar levels and control insulin sensitivity. This contradicts the long-held belief in the scientific community that beta cells need other cells inside the pancreas to do their job of secreting insulin properly.
The results of the study, published in Nature Metabolism on August 21, support efforts to develop treatments for diabetes by generating populations of beta-cell-like cells without the presence of other cells, such as those from pluripotent stem cells differentiated in the laboratory or by reprogramming other cells to become insulin-producing cells in the body.
Who controls blood sugar?
To meet the body’s changing metabolic needs, blood sugar levels must be maintained within a narrow range. Rapid and precise regulation of blood sugar levels requires a complex interplay of hormones and neurotransmitters secreted into the blood by multiple organs, including the brain, liver, intestines, adipose tissue, muscle, and pancreas.
Pancreatic cells play a key role in stabilizing blood sugar by secreting various hormones, most notably insulin, which stimulates the uptake of sugar from peripheral tissues. Insulin secretion is tightly regulated by beta cells in response to blood sugar levels, but is also influenced by stimuli originating from alpha cells, delta cells, and gamma cells in the pancreas.
New study tells you other cells aren’t necessary
The team led by Pedro Herrera, professor in the Department of Genetic Medicine and the Diabetes Center at the Faculty of Medicine of the University of Geneva, discovered the amazing ability of pancreatic cells to change their function. If beta cells die prematurely, cells that are normally responsible for producing other hormones such as glucagon or somatostatin can start producing insulin.
It was accepted that beta cells could not function properly without the presence of other hormone cells such as alpha, delta and gamma cells that were grouped together within the pancreas.
“To investigate this, we created mice that, upon reaching adulthood, could selectively eliminate all non-beta cells in the pancreas to observe how beta cells were able to regulate blood sugar levels,” explains Marta Pérez-Francis, a researcher in Pedro Herrera’s lab and lead author of the work. “In a surprising result, our mice were not only able to manage their blood sugar levels effectively, but were even healthier than other mice.”
These mice showed improved insulin sensitivity in all target tissues, even when fed a high-fat diet or tested for insulin resistance, a key marker of diabetes, particularly in adipose tissue. But why?
“There is an adaptation process in which the body recruits other hormone cells from outside the pancreas to cope with the sudden drop in glucagon and other pancreatic hormones, but this shows that cells other than beta cells in the pancreas are not necessary to maintain glycemic homeostasis,” explains Pedro Herrera, according to EurekAlert. These findings are surprising and challenge the prevailing idea until now.
Emerging new therapies
About 2% of pancreatic cells change function in the absence of insulin. The challenge now is to identify a molecule that can trigger and expand this transformation, so another strategy would be to differentiate stem cells in the laboratory to produce new beta cells before transplanting them into patients.
Pedro Herrera is excited about their findings: “Our results demonstrate that strategies that focus on insulin cells can really work. The next stage of our work will involve determining the molecular and genetic profile of non-beta cells from individuals with and without diabetes, with the hope of identifying elements that might make it possible to induce the conversion of these cells in the pathological context of diabetes.”