Scientists at Cornell University have discovered that a loss of a key pancreatic cell type might be a contributor to diabetes

Scientists at Cornell University have discovered that a loss of a key pancreatic cell type might be  ...

A transplanted pseudoislet made from CD63hi beta cells. Credit: Weill Cornell Medicine

A recent study conducted by Weill Cornell Medicine researchers has revealed that the loss of a highly productive type of beta cell in the pancreas might contribute to the development of diabetes.

The research, which was recently published in Nature Cell Biology, was led by Dr. James Lo, an associate professor of medicine at Weill Cornell Medicine. One group, named cluster 1, stood out due to its superior insulin production and sugar metabolism abilities.

"Before this, people assumed that a beta cell was a beta cell, and they just counted total beta cells," said Dr. Lo, who is also a member of the Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The researchers from Weill Cornell Medicine, Doron Betel, Jingli Cao, Geoffrey Pitt, and Shuibing Chen, all worked together.

The researchers studied single-cell transcriptomics to examine all of the genes expressed in individual mouse beta cells, then used the information to group them into four types. Additionally, the cluster 1 beta cells were distinguished from the other beta cell types by its high expression of the CD63 protein.

"CD63 expression provided us a means to identify the cells without destroying them," he said.

When the group examined human and mouse beta cells, they discovered that cluster 1 beta cells with high CD63 gene expression produce more insulin in response to sugar than the three other types of beta cells with low CD63 expression.

"We believe they may support the majority of the insulin production, thus their demise might have profound consequences."

The number of insulin-producing beta cells decreased in mice fed an obesity-inducing, high-fat diet, and mice with type 2 diabetes.

"You may have less insulin production, which may play a major role in diabetes development," says the author.

Type 2 diabetes mice received high CD63 production beta cells that restored blood sugar levels to normal. However, removing the transplanted cells caused high blood sugar levels to return. Transplanting low CD63 production beta cells into the mice did not restore blood glucose to normal levels. Instead, the transplanted low CD63 beta cells appeared to be dysfunctional.

Dr. Lo noted that the discovery may have implications for the use of beta cell transplants to treat diabetes. For example, it might be beneficial to transplant only high-tech CD63- beta cells. It might also be feasible to transplant fewer high-tech cells, according to Dr. Lo. His research.

Next, Dr. Lo and his colleagues want to know what happens to the high CD63-producing beta cells in diabetic mice, and how to prevent them from dissolving.

“If we can achieve the goal of keeping them around longer, so they are still alive, and they are capable of functioning,” he said.

Athletes want to know how existing diabetes treatments affect all types of beta cells. GLP-1 agonists, which help increase insulin release in diabetics, interact with high and low CD63-producing beta cells.

“Our research also suggests that GLP-1 agonists may be a way to increase the number of low-CD63-producing beta cells,” Dr. Lo said.

Alfonso Rubio-Navarro, Nicolás Gómez-Banoy, Friederike Dündar, Lunkun Ma, Norihiro Imai, Angie Chi Nok Chong, David E. Cohen, Shuibing Chen, Mark O. Huising, James C. Lo, 16 March 2023, Nature Cell Biology. DOI: 10.1038/s41556-023-01103-1

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