Identifying the islet heterogeneity (cell types and the proportion of each subpopulation) and their relevance to function and disease will lead to fundamental information for the prevention and therapies of diabetes. Here, we introduce a single-cell phenotypic essay on the heterogeneity within individual pancreatic islets by using the combination of synchrotron infrared microspectroscopy and quantitative calculation. In a mouse model, the cellular heterogeneities at both the whole pancreas and single intact islet level were identified. The variation of biochemical phenotypes successfully subdivided islet cells into five main groups and quantitatively determined their proportion. These findings not only demonstrate single-cell infrared phenomics as a value complementary technique and strategy for the description of cellular heterogeneity within the pancreatic islets but also provide a quick, label-free optical platform for investigating phenotypic heterogeneity at the small-organelle level with single cell resolution.
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http://dx.doi.org/10.1016/j.aca.2023.341185 | DOI Listing |
Cells
March 2025
Medizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, Germany.
The engraftment of transplanted islets depends on the rapid establishment of a novel vascular network. The present study evaluated the effects of cord blood-derived blood outgrowth endothelial cells (BOECs) on the viability of neonatal porcine islets (NPIs) and the post-transplant outcome of grafted NPIs. Dispersed NPIs and human BOECs were reaggregated on microwell cell culture plates and tested for their anti-apoptotic and pro-angiogenic capacity by qRT-PCR and immunohistochemistry.
View Article and Find Full Text PDFBMJ Open Diabetes Res Care
March 2025
Department of Clinical Sciences, Lund University Faculty of Medicine, Lund, Sweden.
Introduction: In type 2 diabetes (T2D), beta cell failure is often associated with islet inflammation driven by the innate immune response, with macrophages playing a significant role. However, the composition and phenotype of lymphoid immune cells in the islets of individuals with T2D have not been extensively studied. This study aims to characterize and compare the presence, phenotype, and frequency of islet-associated lymphocytes-specifically T, B, and natural killer (NK) cells-in patients with T2D and non-diabetic organ donors.
View Article and Find Full Text PDFCompr Physiol
April 2025
Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
This review focuses on p21-activated kinase 1 (Pak1), a multifunctional, highly conserved enzyme that regulates multiple downstream effectors present in many tissues. Upstream signaling via Ras-related small G-proteins, Cdc42/Rac1 promotes the activity of Pak1. Our hypothesis is that this signaling cascade is an important element in communication among the myocardium, adipose tissue, and pancreatic β-cells.
View Article and Find Full Text PDFDiabetologia
March 2025
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Aims/hypothesis: Components of the insulin processing and secretion pathways remain incompletely understood. Here, we examined a genome-wide association study (GWAS) signal for plasma proinsulin levels. Lead GWAS variant rs150781447-T encodes an Arg279Cys substitution in TBC1 domain family member 30 (TBC1D30), but no role for this protein in insulin processing or secretion has been established previously.
View Article and Find Full Text PDFElife
March 2025
Ache Lab, Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Am Hubland, Würzburg, Germany.
Insulin plays a critical role in maintaining metabolic homeostasis. Since metabolic demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments are mediated by different pathways, most prominently the blood glucose level, but also by feedforward signals from motor circuits and different neuromodulatory systems.
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