Lipids play multiple roles in normal and pathological functions of cells and organs including structural, energy balance, cell signaling and maintenance of homeostasis. In the pancreatic islets, lipids have been implicated in regulating aspects of membrane fusion and hence insulin (and other hormones) release. Imbalances in lipid metabolism, accumulation, and localization have been associated with T2D progression. Wide variety of lipid classes are observed in the pancreatic islets including glycerophospholipids, glycerophospholipids, and ceramides. Complex cellular organization of these structures suggests that lipid profiles of different cell types or even functional cell subtypes, may not be the same. In this work, high throughput single cell mass spectrometry (MS) was used to analyze cellular populations of isolated human individual pancreatic islets received from the Human Pancreas Analysis Program (UPenn). Besides lipids, peptide markers for the canonical islet cell types are observed in the same cells allowing us to associate specific lipid profiles with cell types. For example, beta cells exhibited larger signals matching to PC(34:1), SM(d34:2), and SM(d38:1). Epsilon cells, among others, have enriched SM(d42:2)- and SM(d42:1)-like signals. Alpha cells demonstrate the most complex lipid profile with 10 lipid species exhibiting higher relative intensities. Current work involves matching the single cell lipid peaks to specific lipids, and understanding how the high plasticity of lipid profiles in each cell type track disease progression. These observations create a base for further investigation of roles of lipids in normal and pathological functioning of the pancreatic islets.


S. Rubakhin: None. J.V. Sweedler: None.


American Diabetes Association/Pathway to Stop Diabetes (1-18-VSN-19 to J.V.S.)

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