Chemical profiles and heterogeneity of islets may contribute to diabetes, but this chemical heterogeneity has been difficult to study. While significant progress has been achieved in uncovering of transcriptional diversity of cells composing pancreatic islets, the direct measurement of the hormones and metabolites has been difficult. We have created new approaches using direct matrix assisted laser desorption/ionization mass spectrometry (MALDI MS) to investigate the metabolite, and peptide contents of human pancreatic islets and of populations of individual islet cells. As illustrated in Figure 1, we observe multiple molecular features in the m/z 20-7000 mass range, including expected peptide hormones, lipids and transmitters. The specific peptide profiles vary cell to cell. Besides the expected peptide hormones, we also observe rarer peptides such as apelin and spexin. We also characterize unusual peptide profiles from rare cells that remain to be characterized. We observe five major cell types including a group of cells that appear only to contain thymosin beta four. We are extending our measurements to important molecules such as dopamine and d-serine. We are in the process of determining how the peptide hormones and metabolites co-localize, and are exploring how the molecular portraits change during disease progression.


J.V. Sweedler: None.


American Diabetes Association/Pathway to Stop Diabetes (1-18-VSN-19)

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