New Insights on How β-Cell Subtypes Impact the Development of Type 2 Diabetes

Recent research sheds light on the critical role of pancreatic β-cell subtypes in the progression of type 2 diabetes (T2D). β-cells, responsible for producing insulin, are not uniform; they consist of various subtypes with differing functions, viability, and capacities to proliferate. Understanding these differences is vital because the proportion and health of β-cell subtypes influence overall β-cell mass and the body's ability to regulate blood glucose levels.

A team from Vanderbilt University, including Professors Guoqiang Gu and Ken Lau, along with Associate Professor Emily Hodges, has developed innovative methods to track β-cell subtypes over time, overcoming traditional limitations of studying only fully mature cells at a single point. Their approach involves indelibly marking progenitor cells—the source of β-cell subtypes—based on their gene expression patterns, enabling detailed observation of cell differentiation, maturation, and function throughout various stages.

Their recent study, published in Nature Communications, revealed several key findings:

1. β-cell progenitors originating from embryonic stages give rise to subtypes with different levels of functional fitness in adults, suggesting potential avenues for manipulating cell development to reduce diabetes risk.
2. Maternal nutrition, especially a high-fat diet and obesity, significantly affects the composition of β-cell subtypes in offspring, with malnutrition decreasing the proportion of high-functioning β-cells and increasing diabetes susceptibility.
3. The β-cell subtypes identified in mouse models have parallels in the human pancreas; notably, high-fitness subtypes are often reduced in individuals with T2D, indicating that improving the health and proportion of these subtypes could be a therapeutic target.

The research also highlights the importance of epigenetic patterns—such as gene expression markers—in maintaining β-cell subtype identity and function. Future investigations aim to understand how these patterns are established and maintained, opening potential for interventions like dietary supplements during pregnancy to lower diabetes risks in offspring.

This groundbreaking work provides vital insights into β-cell development and functionalities, illustrating pathways to potentially enhance β-cell mass and health through targeted therapies or lifestyle modifications, ultimately aiming to delay or prevent the onset of type 2 diabetes.

For more detailed information, see the original study: Monica E. Brown et al., "Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors," Nature Communications (2025). DOI: 10.1038/s41467-025-60831-0.