β-Cell-Derived Extracellular Vesicles Boost β-Cell Functionality in Human Pancreatic Islets | Biomaterials Research Extracellular vesicles (EVs) are emerging therapeutic tools in nanomedicine, yet their effects in 2-dimensional (2D) versus 3D diabetes models remain underexplored. Unlike synthetic nanoparticles, EVs...

Boucenna et al. present a proof-of-concept study focused on exploring the potential of extracellular vesicles derived from human EndoC-βH1 cells to enhance β-cell functionality and insulin secretion. 🧪
#PancSky

spj.science.org/doi/10.34133...

Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing β cells, driven in part by endoplasmic reticulum (ER) stress an…

Li et al. demonstrate that elevated MANF levels protected against multiple low-dose streptozotocin-induced hyperglycemia, preserved β cell mass, enhanced proliferation, and reduced β cell DNA damage responses and islet lymphocyte infiltration. 🧪
#PancSky

www.sciencedirect.com/science/arti...

Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles Effective therapies for type 1 diabetes (T1D) must both restrain immune hyperactivity and reduce β cell susceptibility to destruction. We describe a l…

Enriquez et al. describe a lipid nanoparticle platform for β cell-enriched mRNA delivery that can be further augmented by conjugation to enhanced glucagon-like peptide-1. 🧪
#PancSky

www.sciencedirect.com/science/arti...

Cambraia et al. suggest that calorie restriction improves glucose homeostasis and remodels the islet microenvironment to promote beta cell longevity through a pro-tolerogenic immune microenvironment, which reduces the risk of autoimmune diabetes. 🧪
#PancSky

www.biorxiv.org/content/10.6...

RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity - Cell Death & Disease Cell Death & Disease - RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity

Contreras et al. suggest that receptor interacting protein kinase 1 (RIPK1) promotes β-cell demise in response to cytokine and autoimmune stress via actions on gene expression and kinase signaling. 🧪
#PancSky

www.nature.com/articles/s41...

Here the authors assess a large amount of human tissue using mass cytometry to assess pancreatic ductal cell/endocrine cell coexpression www.biorxiv.org/content/10.6... #PancSky

Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes - Cell Death & Differentiation Cell Death & Differentiation - Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes

Yi et al. show that combining large-scale single-cell and bulk RNA-seq analyses can identify key features underlying alpha-cell resistance to diabetes-related damage. 🧪
#PancSky

www.nature.com/articles/s41...

Transient ER stress cell-autonomously promotes beta cell cycling in mice - Diabetologia Aims/hypothesis Regenerating endogenous pancreatic beta cells is a potentially curative yet currently elusive strategy for diabetes therapy. Mimicking the microenvironment of the developing pancreas a...

Important study of ER stress link and beta cell proliferation. Even induced GFP overexpression could cause a mild increase in ER stress, which provides food for thought for transgenic overexpression of copious amount and proper study design. Great work! #PancSky link.springer.com/article/10.1...

Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity C3 is highly expressed in human and rodent pancreatic islets, which secrete insulin to regulate blood glucose homeostasis. We have previously shown th…

King et al. generated a beta-cell-specific complement C3 knockout mouse to test whether cell-intrinsic C3 is required for beta-cell function in a whole animal model. 🧪
#PancSky

www.sciencedirect.com/science/arti...

Protective IFIH1 variant reduces immune-mediated islet stress and dysfunction in a type 1 diabetes genetic background Genome-wide association studies (GWAS) have linked dozens of genetic loci to type 1 diabetes (T1D). The IFIH1 gene, which encodes the double-stranded RNA sensor MDA5, is one such locus. The E627* sing...

Veronese-Paniagua et al. hypothesised that stem cell-derived islets harbouring a protective IFIH1 variant exhibit a dampened immune response, which protects β cells from stress-induced dysfunction, identity loss, and death. 🧪
#PancSky

www.biorxiv.org/content/10.6...

Restoration of PKM1 improves functional maturation of human stem-cell derived-β cell by regulating PEP metabolism - Nature Communications Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation o...

Lin et al. reveal a critical role of pyruvate kinase M1-regulated PEP metabolism in stem cell-derived-β-cell functional maturation and highlight the importance of metabolic reprogramming for advancing stem cell-based therapies for diabetes. 🧪
#PancSky

www.nature.com/articles/s41...

GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function - Nature Communications Following its internalisation, active endosomal GLP-1R engages with VAPB and SPHKAP at ER membrane contact sites to assemble a local cAMP/PKA condensate for the control of MICOS complex phosphorylatio...

Austin et al. show that GLP-1RA drives GLP-1R-positive endosomes to ER-mitochondria contact sites, where active GLP-1R associates with the ER tether VAPB and engages SPHKAP, an AKAP genetically linked to T2D and adiposity. 🧪
#PancSky

www.nature.com/articles/s41...

Alpha cell MHC-I expression recruits cytotoxic CD8+ T cells during human aging and type 2 diabetes Aging is a major risk factor for type 2 diabetes (T2D), driven in part by loss of beta cell identity and function due to stress and islet inflammation. Calorie restriction (CR) improves metabolic heal...

Schleh et al. demonstrate that ageing alpha cells exhibit an active inflammatory phenotype characterised by increased IFNα/γ signalling, which activates MHC-I expression and promotes CD8+ T-cell accumulation in both mouse and human islets. 🧪
#PancSky

www.biorxiv.org/content/10.1...

Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells - Nature Communications Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacem...

Lietzke et al. demonstrate that pluripotent stem cell-derived β cells exhibit reduced oxidative and mitochondrial fatty acid metabolism compared to primary human islets, which is related to limitations in key mitochondrial transcriptional networks. 🧪
#PancSky

www.nature.com/articles/s41...

A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes - Nature Immunology The authors identify a Cys→Ser transformation (C19S) in insulin leading to neoepitope presentation and CD4⁺ T cell autoreactivity in type 1 diabetes. Inflammation and oxidative stress enhanced C19S tr...

Srivastava et al. applied a β-cell degranulation strategy coupled with HLA-II immunopeptidome profiling to systematically identify islet-derived peptides presented in human peripheral blood. 🧪
#PancSky

www.nature.com/articles/s41...

The G Protein-Coupled Receptor GPR31 Promotes Pro-inflammatory Responses in Pancreatic Islets and Macrophages In type 1 diabetes (T1D), the innate and adaptive immune systems attack and eventually destroy the insulin-secreting pancreatic β cells. During this process, β cells activate inflammatory signaling pa...

Kaylan et al. generated mice with genetic deletion of Gpr31b to test the hypothesis that the G protein-coupled receptor GPR31 promotes β-cell and macrophage inflammatory signaling and contributes to β-cell dysfunction in diabetes. 🧪
#PancSky

www.biorxiv.org/content/10.1...

Islet-intrinsic sex differences in inflammatory signaling contribute to autoimmune diabetes susceptibility Whereas most autoimmune diseases exhibit female predominance, type 1 diabetes (T1D) occurs more frequently in males after puberty, suggesting a role for sex hormones in disease modification. Because i...

Webster et al. found that male islets exhibit a more aggressive response to proinflammatory cytokines, characterized by greater induction of interferon signaling and suppression of developmental signaling compared to female islets. 🧪
#PancSky

www.biorxiv.org/content/10.1...

Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing Glucagon (Gcg)-expressing pancreatic α cells play pivotal roles in maintaining glucose and amino acid homeostasis; however, the cellular heterogeneity…

Shimizu et al. show that single-cell transcriptomics using a time-resolved reporter mouse line demonstrated novel features of temporal and transcriptional heterogeneity of developing α cells. 🧪
#PancSky

www.sciencedirect.com/science/arti...

Nguyen et al. identified a novel ROS-Ca2+ overload-mTORC1 cytopathic mechanism that underlies impaired autophagy and proposed various protective strategies to correct or relieve pathogenic alteration in β-cell lipotoxicity. 🧪
#PancSky

insight.jci.org/articles/vie...

#PancSky

Evaluation of the pharmacological cathepsin S inhibitor LY3000328 on autoimmune diabetes in mice There is an emerging role for the lysosomal protease cathepsin S (CTSS) in the pathogenesis of type 1 diabetes (T1D). This is supported by key finding…

Frørup et al. aimed to evaluate cathepsin S as a treatment target in type 1 diabetes by examining the effects of oral administration of the potent and selective Ctss inhibitor LY3000328 on autoimmune diabetes and glucose tolerance in the NOD mouse. 🧪
#PancSky

www.sciencedirect.com/science/arti...

Deadline Dec 5. Fellowships: Pancreatic Cancer Detection/AI—& more.
Scadenza: 5 dicembre. Borse di ricerca sul Cancro al pancreas/intelligenza artificiale—e molto altro.
@Columbia. Details: tinyurl.com/iafellow26 #PancreaticCancerAwarenessMonth, #WorldPancreaticCancerDay, #PancSky

In the afternoon sessions, we discuss work packages 1 – 3, first each progress separately, then jointly in a planum discussion.
1️⃣ Patient cohorts & sample collection
2️⃣ #liquidbiopsy diagnostis
3️⃣ AI analysis & data management

#PancSky

Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells - Diabetologia Aims/hypothesis Residual pancreatic beta cells in type 1 diabetes show reduced insulin production but the mechanisms remain unclear. Beta cells undergo stress responses during type 1 diabetes, includi...

Findings by Préfontaine et al. suggest that the expression of proinsulin-processing enzymes and the production of insulin are sustained in both chemically induced DNA damage-related senescence and in endogenous senescent adult human beta cells. 🧪
#PancSky

link.springer.com/article/10.1...

Small things matter: Lack of extraislet β cells in type 1 diabetes Early loss of small extraislet β cells in children with type 1 diabetes could explain age-related differences in disease.

Murrall et al. used archival, immunolabeled 2D pancreas sections to assess morphological endocrine object parameters in donors with or without #type1diabetes, varying in age and disease duration. 🧪
#PancSky

www.science.org/doi/full/10....

Cool work using spatial transcriptomics among other methods to discover new mesenchyme signaling on developing pancreas niche #PancSky

Human stem cell-derived β cells expressing an optimized CD155 reduce cytotoxic immune cell function for application in type 1 diabetes Engineered β cells with a mutant CD155 help evade immune attack, offering a promising therapeutic approach for type 1 diabetes.

Brown et al. demonstrated that stem cell–derived β cells can be engineered to express CD155 to preferentially promote T cell coinhibitory signaling through the CD155/TIGIT axis and restrain both NK cell and T cell activation. 🧪
#PancSky

www.science.org/doi/10.1126/...

Benchmarking porcine pancreatic ductal organoids for drug screening applications | EMBO Molecular Medicine imageimageState-of-the-art single-cell RNA sequencing and proteomics approaches were employed to benchmark porcine and human pancreatic ductal organoid systems for use as a drug screening and testing ...

Happy to share that our preprint is now published at @embomolmed.org! We expanded on the benchmark of porcine ductal organoids by a pretty extensive proteomics dataset to compare organoids derived from different developmental stages of the pig #devbio #PancSky www.embopress.org/doi/full/10....

Proinflammatory circulating extracellular vesicles from type 1 diabetes patients contribute to beta cell cytotoxicity and disease pathogenicity In Type 1 diabetes (T1D), β-cell loss and autoimmunity initiate years before disease diagnosis. However, the mechanisms remain unknown. Here, we investigated the role and mechanisms of circulating ext...

Guthalu Kondegowda et al. investigated the role and mechanisms of circulating extracellular vesicles on #type1diabetes pathogenesis and β-cell cytotoxicity. 🧪
#PancSky

www.biorxiv.org/content/10.1...

Human pancreatic organoids derived from pluripotent stem cells recapitulate pancreatic organogenesis Pancreas organogenesis relies on sequential interactions between the pancreatic epithelium and surrounding mesodermal cell types that initiate epithelial budding and branching to form a complex ductal...

So cool embryonic pancreas epithelium modeling using stem cells by the Wells lab! #PancSky
www.biorxiv.org/content/10.1...