If it has seemed like more people you know are developing diabetes, you are right. The diabetes epidemic is not called that for nothing: According to the American Diabetes Association, over 10 percent of the U.S. population—approximately 38.4 million people— had diabetes in 2021 , and 1.2 million more people get diagnosed each year.
Type 2 diabetes occurs when your body develops a resistance to insulin, the hormone that helps regulate glucose levels in your blood. Insulin is secreted by pancreatic cells called β-cells, and, in T2D, they ramp up insulin production to try to regulate blood glucose levels, but even that is insufficient and the β-cells eventually become exhausted over time. Thanks to their importance, the functional β-cell mass, or the total number of β-cells and their function, determines a person's risk of diabetes.
Β-cells are not homogeneous even within a single individual and consist of different "subtypes," each with their own secretory function, viability, and ability to divide. In other words, each β-cell subtype has a different level of fitness, and the higher, the better. When diabetes develops, the proportions of some β-cell subtypes are changed. But a key question remains: Are the proportion and fitness of different β-cell subtypes altered by diabetes or are the changes responsible for the disease?
Cue Guoqiang Gu, Emily Hodges, and Ken Lau, Vanderbilt faculty members who set out to answer these questions, and more. Their recent work, published in Nature Communications , is a step toward determining whether it is possible to enhance functional β-cell mass to reduce the risk of T2D. Gu and Lau are professors of cell and developmental biology and Hodges is an associate professor of biochemistry.
Studying β-cell subtypes is challenging. The most common method of studying them is called "terminal examination of samples at single-cell levels," which means that scientists can only study particular β-cell subtypes once, and only when they are fully developed, which precludes them from examining a specific cell subtype at distinct stages in differentiation, maturation, proliferation, senescence, death, and more. If they could monitor β-cells at multiple stages, researchers could better understand how cells' states drift over time or under different physiological conditions.
Gu, Hodges, and Lau developed a method that avoids this problem by indelibly marking the progenitor cells that give rise to the β-cell subtypes with different gene expression combinations. The markings enabled the researchers to track the same β-cell subtypes over time at different stages, allowing them to tackle questions about β-cell subtypes with confidence.
The Nature Communications paper yielded three primary results:
- Progenitor cells that give rise to β-cells with different gene expression markers in embryonic mice give rise to β-cell subtypes with varying levels of fitness in adult mice. This helps researchers understand how different β-cell subtypes arise and could help them one day manipulate progenitor cells to favor certain subtypes over others and decrease the risk of diabetes.
- The nutrients that mother mice consume have a clear effect on the proportion of high-fitness to low-fitness β-cell subtypes in their pups. For example, when mother mice were on a high-fat diet and obese, their pups had fewer β-cells that responded better to glucose levels. What this model for obesity shows is that maternal obesity increased the risk of diabetes for the offspring. This gives scientists and clinicians a better understanding of the hereditary factors and maternal medical history that can predispose someone to diabetes.
- The β-cell subtypes identified in mice have parallels in the human pancreas. In fact, the β-cell subtype predicted to have higher fitness in humans was observed to be reduced in patients with T2D. Although the findings from animal studies are not always directly applicable to humans and human health, these results suggest that β-cell subtypes in mice can be helpful for understanding human biology and risk of diabetes.
The researchers now hope to explore how the epigenetic patterns (the gene expression markers mentioned above) are built and maintained in the different β-cell subtypes and how disturbing those patterns impacts β-cell fitness.
"Thanks to this and other research, it may be possible to one day create a diet supplement for pregnancy that could reduce the risk of diabetes for babies," Gu said.
Additional questions remain unanswered that tie into potential diabetes therapies: does modulating DNA methylation (an epigenetic marker) improve the functional quality of human embryonic stem cell–derived, β-like cells? If so, can those β- and β-like cells be used for transplantation-based diabetes therapies in which T2D patients receive β-cells of higher fitness?
Stay tuned.
Go deeper
The paper " Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors " was published in Nature Communications in July 2025. The paper was led by co-first authors Monica Brown, Verda Miranda, Simone Nevills, and Ruiying Hu.
Funding
This research used funds from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, and the National Institute of General Medical Sciences.
School of Medicine Basic Sciences shared resources
This research made use of the Cell Imaging Shared Resource and the Vanderbilt Genome Editing Resource.
