Surprising discovery: There are two subtypes of insulin-producing beta cells in our pancreas, new analysis reveals. These two subspecies differ in shape and size, the extent of their epigenetic appendages, and their response to blood sugar. The ßHI subtype releases insulin more quickly and is more common in people with type 2 diabetes. This might offer new approaches for diagnosis and therapy, according to the team in the journal Cell Metabolism.
The beta cells in our pancreas are essential for controlling blood sugar levels. When needed, they produce the blood sugar hormone insulin, which promotes the absorption of glucose from the blood into the cells. This ensures that neither too much nor too little blood sugar circulates in the body. In the case of diabetes, however, this system is thrown out of balance: in type 2 diabetes, the beta cells are destroyed by an autoimmune reaction, in type 2 diabetes they gradually cease to function due to overload.
Without the beta cells, however, we cannot control our blood sugar levels. If they are no longer working, insulin must therefore be supplied from outside. It is all the more important to know the function, peculiarities and vulnerabilities of the beta cells as precisely as possible.
Are there different types of beta cells?
This is where Erez Dror from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg and his colleagues come in. They have followed a lead that goes back to the 1960s. Even then, scientists had established that not all beta cells are the same. “The early studies found differences in the glucose threshold, in the way calcium is used and in insulin secretion,” the researchers report
But whether these were just random variations or whether there might be different subspecies of beta cells remained an open question. To answer this question, Dror and his team have now analyzed the epigenome of beta cells from mice and human pancreas cell cultures in more detail. These attachments to the DNA affect gene activity by directly blocking the reading of a gene or by tightening the packaging of the strand of genetic material at this point. This also shuts down the affected gene.
Two subtypes distinguishable
The analyzes showed that the beta cells form two subgroups that can be clearly distinguished on the basis of their epigenome. “All the cells are a little different, but these two beta cell subtypes are clearly and consistently separated,” says senior author J. Andrew Pospisilik of the Van Andel Institute in the US. The main feature of these subtypes is the concentration of the epigenetic marker H3K27me3. This attaches itself to the histone proteins that are part of the DNA packaging and thereby shuts down genes.
“We found that the beta cells are divided into two epigenetically different subgroups: one with a high (ßHI) and one with a low (ßLO) content for this specific histone modification,” reports Dror. Further investigation revealed that the ßHI and ßLO subtypes also differ in shape, size, internal structure and function.
Differences in response to blood sugar
Interesting: The two beta cell subtypes react slightly differently to an increase in blood sugar levels. The rounder ßHI cells release large amounts of insulin very quickly when glucose levels are high. The ßLO cells, on the other hand, react more slowly and seem to be more important for the longer-term control and stabilization of the blood sugar level. “They are specialists, each with their own role in insulin production,” explains Pospisilik.
As the team found, the proportions of the two beta cell subtypes are not the same in all mice and humans: In type 2 diabetes, there are more rapidly and strongly reacting ßHI cells in the pancreas. The slower ßLO cells, on the other hand, have a lower proportion than normal.
New approaches to diabetes therapy
The discovery of the two beta cell subtypes might thus also provide new approaches for the diagnosis and therapy of this form of diabetes. “If we better understand the two beta cell types and their relationship to each other, this might give us a clearer picture of diabetes and also new options for treatment,” says Pospisilik. Unlike DNA, epigenetic appendages can be modified by external factors, such as diet and lifestyle influences, but also certain chemical agents.
“The crucial thing is that epigenetic changes can be reversed,” says Pospisilik. This opens up new possibilities for therapy. (Cell Metabolism, 2023; doi: 10.1016/j.cmet.2023.03.008)
Source: Van Andel Research Institute, Max Planck Institute of Immunobiology and Epigenetics
