Using an epigenetic approach, scientists report finding two distinct subtypes of insulin-producing beta cells, each with characteristics that may help increase understanding of Type 1 and Type 2 diabetes.
The two cell types—described by study authors as ßHI and ßLO—differ in specific function, size, shape, and epigenomic features, among other characteristics. They also exhibit contrasting patterns of surface markers, which help control chemical messages. ßHI cells appear to be more prevalent in Type 2 diabetes.
Like transcription factors, epigenetic marks tell genes when to activate. The researchers say these new findings could affect future diabetes treatments, in several ways, such guiding the adjustment of the ratio of ß cell subtypes in transplants to ensure optimal function.
The team was led by researchers at Van Andel Institute and Max Planck Institute of Immunobiology and Epigenetics. Their work was published last week in Cell Metabolism, and the lead author was Max Planck’s Erez Dror.
Beta, or ß, cells control the body’s metabolic balance. They are the only cells capable of producing insulin, which regulates blood sugar levels by designating dietary sugar for immediate use or storage.
In Type 1 diabetes, ß cells are attacked by the body’s own immune system, rendering them unable to produce insulin.
Type 2 diabetes arises from insulin resistance. The resulting excess blood sugar from a person’s diet causes ß cells in the pancreas to work overtime. Eventually, these cells can no longer keep up and blood sugar concentrations can rise to dangerously high levels.
Both diseases are treated by enhancing insulin action, either by providing insulin itself, or by augmenting its activity and release into the blood. Some people with Type 1 diabetes may elect to have a ß cell transplant, an experimental procedure in which functioning cells from a donor are implanted into the pancreas.
“All cells vary in some way, but these two ß cell subtypes are discretely and consistently different from one another. This indicates that they serve two different but necessary functions as insulin producers. They are specialists, each with their own roles,” said J. Andrew Pospisilik PhD, a Van Andel Institute professor and senior author of the study.
Importantly, the subtypes can be separated by the presence or absence of a protein called CD24, which acts as a marker that allows targeting of one type and not the other. This distinction may inform development of more precise diabetes treatment strategies and offers a critical tool that enables diabetes researchers to better study each cell type in depth.
The findings could also reshape what is known about how ß cells develop early in life. ß cells are among the longest-lived cells in the body, with lifespans of 30 to 40 years. Like all cells, the earliest ß cells arise from stem cells. This process is largely guided by transcription factors, which switch genes “on” and “off.”
In ß cells, the team previously identified an epigenetic mark called H3K27me3 as a key driver of differentiation. In this new study, they found that dosage of the same mark controls ßHI versus ßLO numbers and, as a result, offers a new target for potential new diabetes treatments.
“The beauty of this mechanism is its novelty—it’s purely driven by epigenetics with no help from transcription factors,” Pospisilik said. “The key here is that epigenetic changes can be reversed, which opens a whole host of questions with implications for treatment.”