ArticlePhysiological reports2018
Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets.
Article in Physiological reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- α/β-Hydrolase Domain Containing 5 Supports Glucose-Stimulated Lipolysis and Insulin Secretion in Pancreatic β-Cells.Diabetes · 2026Article
- Acute Inhibition of Adipose Triglyceride Lipase by NG497 Dysregulates Insulin and Glucagon Secretion From Human Islets.Endocrinology · 2025Article
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Towards a better understanding of diabetes mellitus using organoid models.Nature reviews. Endocrinology · 2023Review
- Utilization of commercial collagens for preparing well-differentiated human beta cells for confocal microscopy.Frontiers in endocrinology · 2023Article
- Development of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus.Human gene therapy · 2022Article
- Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.JCI insight · 2021Article
- Review
- Deciphering the Complex Communication Networks That Orchestrate Pancreatic Islet Function.Diabetes · 2021Review
- Generation of insulin-secreting organoids: a step toward engineering and transplanting the bioartificial pancreas.Transplant international : official journal of the European Society for Organ Transplantation · 2020Review
- Functional analysis of islet cells in vitro, in situ, and in vivo.Seminars in cell & developmental biology · 2020Review
- Article
- In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution.Advanced biosystems · 2020Article
- Lentiviral Mediated Gene Silencing in Human Pseudoislet Prepared in Low Attachment Plates.Journal of visualized experiments : JoVE · 2019Article
- Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets.Physiological reports · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Rodent islets are widely used to study the pathophysiology of beta cells and islet function, however, structural and functional differences exist between human and rodent islets, highlighting the need for human islet studies. Human islets are highly variable, deteriorate during culture, and are difficult to genetically modify, making mechanistic studies difficult to conduct and reproduce. To overcome these limitations, we tested whether pseudoislets, created by dissociation and reaggregation of islet cell suspensions, allow for assessment of dynamic islet function after genetic modulation. Characterization of pseudoislets cultured for 1 week revealed better preservation of first-phase glucose-stimulated insulin secretion (GSIS) compared with cultured-intact islets and insulin secretion profiles similar to fresh islets when challenged by glibenclamide and KCl. qPCR indicated that pseudoislets are similar to the original islets for the expression of markers for cell types, beta cell function, and cellular stress with the exception of reduced proinflammatory cytokine genes (IL1B, CCL2, CXCL8). The expression of extracellular matrix markers (ASPN, COL1A1, COL4A1) was also altered in pseudoislets compared with intact islets. Compared with intact islets transduced by adenovirus, pseudoislets transduced by lentivirus showed uniform transduction and better first-phase GSIS. Lastly, the lentiviral-mediated delivery of short hairpin RNA targeting glucokinase (GCK) achieved significant reduction of GCK expression in pseudoislets as well as marked reduction of both first and second phase GSIS without affecting the insulin secretion in response to KCl. Thus, pseudoislets are a tool that enables efficient genetic modulation of human islet cells while preserving insulin secretion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.