Drs. Doron Betel, Jingli Cao, Geoffrey Pitt and Shuibing Chen at Weill Cornell Medicine coordinated with Dr. Lo to carry out the study.
The private investigators used a technique called single-cell transcriptomics to determine all the genes revealed in specific mouse beta cells and then used that details to group them into four types. The cluster 1 beta cells had a special gene expression signature that included high expression of genes that assist cellular powerhouses called mitochondria to break down sugar and power them to secrete more insulin. Additionally, they could identify the cluster 1 beta cells from the other beta cell types by its high expression of the CD63 gene, which enabled them to utilize the CD63 protein as a marker for this specific beta cell type.
” CD63 expression provided us a way to recognize the cells without ruining them and permitted us to study the live cells,” he said.
When the team looked at both human and mouse beta cells, they discovered that cluster 1 beta cells with high CD63 gene expression produce more insulin in action to sugar than the 3 other kinds of beta cells with low CD63 expression.
” They are extremely high-functioning beta cells,” Dr. Lo said. “We believe they might carry the bulk of the work of producing insulin, so their loss may have extensive effects.”
In mice fed an obesity-inducing, high-fat diet plan and mice with type 2 diabetes, the varieties of these insulin-producing-powerhouse beta cells decreased.
” Because the varieties of cluster 1/high CD63 cells decreased, you might have less insulin production, which may play a major role in diabetes advancement,” he stated.
Transplanting beta cells with high CD63 production into mice with type 2 diabetes restored their blood glucose levels to typical. Removing the transplanted cells triggered high blood sugar levels to return. Transplanting low CD63 production beta cells into the mice didnt restore blood sugar level to normal levels. The transplanted low CD63 beta cells rather appeared dysfunctional.
The discovery might have crucial ramifications for the usage of beta cell transplants to deal with diabetes, Dr. Lo stated. Dr. Los group likewise discovered that people with type 2 diabetes had lower levels of high CD63 beta cells compared to those without diabetes.
Next, Dr. Lo and his colleagues wish to discover out what takes place to the high CD63-producing beta cells in mice with diabetes and how to keep them from disappearing.
” If we can find out how to keep them around longer, making it through and functional, that might lead to much better ways to treat or avoid type 2 diabetes,” he said.
They would also like to study how existing diabetes treatments impact all types of beta cells. GLP-1 agonists, which help increase the release of insulin in individuals with diabetes, connect with low and high CD63-producing beta cells.
” Our study also shows that GLP-1 agonists might also be a way to get the low CD63-producing beta cells to work much better,” Dr. Lo stated.
Referral: “A beta cell subset with improved insulin secretion and glucose metabolic process is minimized in type 2 diabetes” by Alfonso Rubio-Navarro, Nicolás Gómez-Banoy, Lisa Stoll, Friederike Dündar, Alex M. Mawla, Lunkun Ma, Eric Cortada, Paul Zumbo, Ang Li, Moritz Reiterer, Nathalia Montoya-Oviedo, Edwin A. Homan, Norihiro Imai, Ankit Gilani, Chengyang Liu, Ali Naji, Boris Yang, Angie Chi Nok Chong, David E. Cohen, Shuibing Chen, Jingli Cao, Geoffrey S. Pitt, Mark O. Huising, Doron Betel and James C. Lo, 16 March 2023, Nature Cell Biology.DOI: 10.1038/ s41556-023-01103-1.
A transplanted pseudoislet made from CD63hi beta cells. Credit: Weill Cornell Medicine
Multiple types of beta cells produce insulin in the pancreas, assisting to stabilize blood sugar level levels. A recent study conducted by Weill Cornell Medicine investigators has exposed that the loss of an extremely efficient type of beta cell in the pancreas might possibly add to the development of diabetes.
The study, just recently published in Nature Cell Biology, was led by Dr. James Lo, an associate professor of medication at Weill Cornell Medicine, examined gene expression in person beta cells from mice to determine the variety of various beta cell types in the pancreas. The research team found four unique types of beta cells, with one group, called cluster 1, standing out due to their remarkable insulin production and sugar metabolism capabilities. The research study also revealed that the loss of this specific type of beta cell may be connected to the development of type 2 diabetes.
” Before this, people believed a beta cell was a beta cell, and they just counted total beta cells,” stated Dr. Lo, who is likewise a member of the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical. “But this research study informs us it might be important to subtype the beta cells which we require study the role of these unique cluster 1 beta cells in diabetes.”
The research study, just recently published in Nature Cell Biology, was led by Dr. James Lo, an associate professor of medicine at Weill Cornell Medicine, analyzed gene expression in person beta cells from mice to identify the number of various beta cell types in the pancreas. The research study also revealed that the loss of this particular type of beta cell may be linked to the advancement of type 2 diabetes.
In addition, they could distinguish the cluster 1 beta cells from the other beta cell types by its high expression of the CD63 gene, which enabled them to utilize the CD63 protein as a marker for this particular beta cell type.
Transplanting beta cells with high CD63 production into mice with type 2 diabetes restored their blood sugar levels to regular. Dr. Los group likewise found that humans with type 2 diabetes had lower levels of high CD63 beta cells compared to those without diabetes.