In diabetes, beta-cells don’t die, they regress
New experiments in mice are challenging the mainstream-view that the death of beta-cells in the pancreas is the cause of diabetes. The new findings suggest that the cells, which release insulin to control blood sugar levels, revert back to immature forms in response to stress such as aging or even pregnancy.
The work started with the observation that levels of a protein called FoxO1 decrease in beta-cells during early diabetes, but it wasn’t clear whether this was a cause or consequence of the disease. To answer this question the researchers created a strain of mouse whose beta-cells lack the FoxO1 gene. Initially, the mice appeared normal, but after being fed a high-sugar diet, pregnancy or aging, the mice developed low levels of insulin and high levels of glucagon (a pancreatic hormone that counters the effects of insulin) — responses also seen in patients with type-2 diabetes.
To the researchers’ surprise, they found that the beta-cells had not disappeared but had in fact changed into a different cell type. They had reverted from fully mature insulin-making cells to an earlier developmental stage. Some of the cells had changed even further and become glucagon-producing cells, which would explain why people with diabetes have abnormally high glucagon levels. The same changes were observed in other mouse models of type-2 diabetes.
Normally, FoxO1 acts as a sensor of blood sugar levels and responds by activating insulin production. The researchers suggest that conditions that stress the body – such as bad diet or pregnancy – might damage FoxO1 in some way, permanently disabling it. As these new experiments show, this can cause the beta-cells to revert into forms that can’t secrete insulin, resulting in diabetes.
What the research does not reveal is how to reverse the process.