Losing key type of pancreatic cell may contribute to diabetes — ScienceDaily

Losing key type of pancreatic cell may contribute to diabetes — ScienceDaily

Many types of beta cells produce insulin in the pancreas, which helps balance blood sugar levels. The loss of a specific productive type of beta cell may contribute to the development of diabetes, according to a new study by Weill Cornell Medicine investigators.

In the study, published on March 16 in Nature Cell Biology, Dr. James Lo, associate professor of medicine at Weill Cornell Medicine, and colleagues measured gene expression in individual beta cells collected from mice to determine how many different types of beta cells exist in the pancreas. The team discovered four distinct types of beta cells, including one that stood out. The cluster 1 group of beta cells produced more insulin than the other beta cells and appeared to be better able to metabolize sugar. The study also showed that the loss of this type of beta cell may contribute to type 2 diabetes.

“Before this, people thought a beta cell was a beta cell, and they just counted the total beta cells,” said Dr. Lo, who is also a member of the Weill Center for Metabolic Health and Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. “But this study tells us that it may be important to subtype beta cells and we need to study the role of these special cluster 1 beta cells in diabetes.”

said Dr. Doron Betel, Jingli Cao, Geoffrey Pitt and Shuibing Chen at Weill Cornell Medicine collaborated with Drs. Lo to carry out the study.

The investigators used a technique called single-cell transcriptomics to measure all the genes expressed in individual mouse beta cells and then used that information to group them into four types. Cluster 1 beta cells have a unique gene expression signature that includes high expression of genes that help cellular powerhouses called mitochondria break down sugar and give them the energy to secrete more insulin. In addition, they could distinguish cluster 1 beta cells from other beta cell types by its high expression of the CD63 gene, which allowed them to use the CD63 protein as a marker for that specific type. of this beta cell.

“The expression of CD63 gave us a way to identify cells without destroying them and allowed us to study live cells,” he said.

When the team looked at both human and mouse beta cells, they found that cluster 1 beta cells with high CD63 gene expression produced more insulin in response to sugar than the three other beta cell types. with low CD63 expression.

“These are very high-functioning beta cells,” said Dr. Lol. “We think they may carry most of the workload of making insulin, so their loss could have a profound effect.”

In mice fed an obese, high-fat diet and mice with type 2 diabetes, the number of these insulin-producing beta cells decreased.

“Because the numbers of cluster 1/high CD63 cells decrease, you can have less insulin production, which can play a big role in the development of diabetes,” he said.

Transplantation of beta cells with high production of CD63 into mice with type 2 diabetes restored their blood sugar levels to normal. But removing the transplanted cells caused the high blood sugar levels to return. Transplantation of low CD63 producing beta cells into mice did not restore blood sugar to normal levels. The transplanted low CD63 beta cells instead appeared dysfunctional.

The discovery may have important implications for the use of beta cell transplants to treat diabetes, said Dr. Lol. For example, it may be better to transplant only high CD63-beta cells. He noted that it is also possible to transplant fewer of these highly productive cells. Dr.’s team also discovered Lo that people with type 2 diabetes have lower levels of high CD63 beta cells compared to those without diabetes.

Next, Dr. wants to know. Lo and his colleagues what happens to high CD63-producing beta cells in mice with diabetes and how to prevent them from disappearing.

“If we can figure out how to keep them around longer, surviving and functional, that could lead to better ways to treat or prevent type 2 diabetes,” he said.

They also want to study how current diabetes treatments affect all types of beta cells. GLP-1 agonists, which help increase insulin release in people with diabetes, interact with beta cells that produce high and low CD63.

“Our study also shows that GLP-1 agonists can also be a way to make beta cells with low CD63 production work better,” said Dr. Lol.