On March 16, Prof. James Lo, pharmacology cell and developmental biology, and his team published a study identifying different types of cells in the pancreas, an organ responsible for aiding digestion and regulating sugar levels. The research team found one particular cell type to be closely linked to the development of type 2 diabetes.
These cells are classified as ‘beta cells’ — cells in the pancreas that produce insulin, a hormone that maintains normal sugar levels in the body. When the body is unable to produce enough insulin or the cells in the body resist the effects of the insulin, the individual may develop type 2 diabetes over time.
To identify the number of beta cell subtypes present in the pancreas, the research group utilized a technique known as single cell RNA-seq. According to Lo, RNA — the genetic material that helps cells synthesize proteins — is extracted from each individual cell in the pancreas to determine which genes were being expressed.
Lo and his team identified four different beta cell types based on different genes expressed in each type. One type of beta cell, named cluster 1 beta cells, showed better insulin production rates compared to other clusters. However, the team discovered that cluster 1 beta cells had high expression of a gene responsible for producing CD63, a cell protein that acts as a marker for different types of beta cells.
“[CD63] happens to also be a cell surface protein, so that makes it attractive, because we could use that as a tool or marker handle to selectively purify cluster 1 beta cells and separate them from the other beta cell groups,” Lo said.
After determining the different types of beta cells, Lo and his team analyzed the beta cells in two groups of mice: one fed a high-fat diet and one with type 2 diabetes. Although all four beta cell types were found during the early to middle stages of type 2 diabetes, their distribution differed from that of mice with normal diets.
Mice with type 2 diabetes showed low concentration in cluster 1 cells and CD63, resulting in decreased insulin production. The findings indicate that these type of beta cells may be closely related to the development of type 2 diabetes.
Co-author Prof. Doron Betel, computational biomedicine, additionally notes that cluster 1 beta cells with high CD63 levels may have the ability to reverse type 2 diabetes. When the research team transplanted these cells into mice with type 2 diabetes, they observed that the mice’s blood sugar were restored to normal levels.
In the near future, Lo plans to investigate the developmental pathway of these different beta cell types, hoping to potentially induce the cells to develop into a more high-functioning beta cell such as cluster 1 beta cells.
More detailed experiments will be performed to understand how high CD63 cells resist effects of high glucose levels, according to Betel. He added that the next steps include studying the organization of different beta cell types in the pancreas using spatial technology.
“The next wave of genomics studies is using spatial technologies to see the tissue architecture at a single cell level resolution”, Betel said. “And that might be informative to see whether these cells are organized in a very specific spatial form, or if they are just clusters of the cells that are distinct from each other.”
The research has potential medical applications as a diagnostic marker and treatment option for type 2 diabetes patients, according to Lo.
“In terms of the future, if we can understand how we can make more higher-performing beta cells, there can be drugs, nutritional items or other regiments that may help us to obtain more highly functional beta cells for [type 2 diabetes] patients,” Lo said.
Kaitlyn Lee is a staff writer. She can be reached at [email protected]