Hebrew University researchers have introduced a new approach for accurately assessing cell composition in the human pancreas and islets of Langerhans. The pancreas makes hormones to help the body break down and use food. Islets contain several types of cells, including beta cells that make the hormone insulin. Their research addresses a critical need in understanding the genesis of diabetes and offers an alternative to traditional protein marker-based methods.
In a new study published in the journal Diabetes under the title “The study, composition in human pancreas and islets,” Prof. Yuval Dor and his research team, Zeina Drawshy and Dr Agnes Klochendler, introduce a new DNA methylation-based method for accurately assessing cell composition in the human pancreas. Their work addresses a critical gap in diabetes research.
By overcoming limitations of traditional protein marker-based approaches, the study provides a more precise means for identifying specific cell types. The findings offer insights into beta-cell dysfunction across diabetes types and have direct clinical implications, enhancing our understanding of diabetes development and potentially guiding more tailored treatment strategies. This innovative molecular alternative to immunodetection methods holds promise for broader applications in molecular biology and diagnostics.
Current methodologies rely on the detection of protein markers like insulin to identify specific cell types in the pancreas, but variability in protein content under different physiological and pathological conditions poses a significant limitation, complicating the accurate determination of cell numbers.
The study presents the innovative use of cell type-specific DNA methylation markers to overcome these limitations. Methylation is a chemical modification of DNA and other molecules that may be retained as cells divide to make more cells. By identifying genomic loci uniquely demethylated in specific pancreatic cell types, the research team applied targeted PCR to assess the methylation status of these loci in human islet and pancreas specimens. This enabled a precise inference of cell type composition, offering a molecular alternative to traditional immunodetection methods. This made possible a precise inference of cell-type composition, offering a molecular alternative to traditional immunodetection methods.
The researchers looked at groups of islet cells in the pancreas and found that in people with different types of diabetes (pre-type-one, type-one, and type-2 diabetes), the function of a specific type of cell called beta-cells was similar, but it was lower compared to people without diabetes. When they looked at pancreas tissues from people with recent-onset type-one, they found that the beta-cell function was within the normal range, suggesting a problem with these cells. In people with type-two, there were more of another type of cell called alpha-cells, but the beta-cell function was normal. This helps us understand how these cells work in diabetes.
Dor, the lead researcher, explained: “the use of DNA methylation-based analysis not only provides a more accurate assessment of cell types in the human pancreas but also proves invaluable in interpreting insulin secretion assays. This method opens new avenues for understanding pancreas cell composition in both health and disease.”