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Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (<i>GCG</i>, 56%), amylin (<i>IAPP</i>, 52%), insulin (<i>INS</i>, 44%), and somatostatin (<i>SST</i>, 24%). Inhibition of two DEGs, <i>UNC5D</i> and <i>SERPINE2</i>, impaired glucose-stimulated insulin secretion and impacted cell survival in a human β-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.
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http://dx.doi.org/10.26508/lsa.202201376 | DOI Listing |
Front Biosci (Landmark Ed)
August 2025
School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Transcription factors are significant regulators of gene expression in most biological processes related to diabetes, including beta cell (β-cell) development, insulin secretion and glucose metabolism. Dysregulation of transcription factor expression or abundance has been closely associated with the pathogenesis of type 1 and type 2 diabetes, including pancreatic and duodenal homeobox 1 (), neurogenic differentiation 1 (), and forkhead box protein O1 (). Gene expression is regulated at the transcriptional level by transcription factor binding, epigenetically by DNA methylation and chromatin remodelling, and post-transcriptional mechanisms, including alternative splicing and microRNA (miRNA).
View Article and Find Full Text PDFBMJ Open Diabetes Res Care
September 2025
Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg Campus, Frederiksberg, Denmark.
Unlabelled: In mammalian and human life, it is important that the immune system defends against microorganisms. Although there is a huge overlap, innate cells are good against bacteria, whereas T cells are good against viruses, mainly because of antibody production via T helper and B lymphocytes. Toll-like receptor 5 (TLR5) is a regulator; when it is highly expressed, T cells are inhibited, and innate cells are favored.
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 2025
Department of Developmental and Regenerative Biology, iORGANtech Limited Company (Suzhou), Suzhou, 215000, China; Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tia
Progress in uncovering the causes of extrahepatic biliary diseases and developing new therapies has been constrained by the inaccessibility of donor tissue and a lack of experimental models. Although hepatic, intrahepatic biliary, and pancreatic 2D/3D models have been successfully established from pluripotent stem cells (PSCs), in vitro generation of extrahepatic biliary cells remains a major challenge, due to the absence of developmental cues. Here we report a de novo method for directed differentiation of human PSCs (both embryonic and induced) into pancreato-biliary progenitors-like cells (PBPLCs).
View Article and Find Full Text PDFJCI Insight
September 2025
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
In vitro studies have implicated orphan receptor GPRC5B in β-cell survival, proliferation and insulin secretion, but its relevance for glucose homeostasis in vivo is largely unknown. Using tamoxifen-inducible, β-cell-specific GPRC5B knockout mice (Ins-G5b-KOs) we show here that loss of GPRC5B does not affect β-cell function in the lean state, but results in strongly reduced insulin secretion and disturbed glucose tolerance in mice subjected to high fat diet for 16 weeks. Flow cytometry and single-cell expression analyses in islets from obese mice show a reduced β-cell abundance and a less mature β-cell phenotype in Ins-G5b-KOs.
View Article and Find Full Text PDFFront Immunol
September 2025
Chemical and Biological Engineering, Koc University, Istanbul, Türkiye.
Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic beta cells, resulting in lifelong insulin therapy that falls short of a true cure. Beta cell replacement therapies hold immense potential to restore natural insulin production, but they face significant hurdles such as immune rejection, limited donor availability, and long-term graft survival. In this review, we explore cutting-edge advances in genetic engineering, biomaterials, and machine learning approaches designed to overcome these barriers and enhance the clinical applicability of beta cell therapies.
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