ArticleDiabetologia2013
Functional differences between aggregated and dispersed insulin-producing cells.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- LRRC8 channel complexes counterbalance KATP channels to mediate swell-secretion coupling in mouse pancreatic β cells.JCI insight · 2025Article
- Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.Diabetes · 2024Article
- Mechanical and functional characterisation of a 3D porous biomimetic extracellular matrix to study insulin secretion from pancreatic β-cell lines.In vitro models · 2024Article
- Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells.Comprehensive Physiology · 2023Article
- Comparative Study of Two Common In Vitro Models for the Pancreatic Islet with MIN6.Tissue engineering and regenerative medicine · 2023Article
- The endoplasmic reticulum-plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis.Journal of cell science · 2022Article
- The changing view of insulin granule mobility: From conveyor belt to signaling hub.Frontiers in endocrinology · 2022Review
- Process parameter development for the scaled generation of stem cell-derived pancreatic endocrine cells.Stem cells translational medicine · 2021Article
- Enhanced differentiation of human pluripotent stem cells into pancreatic endocrine cells in 3D culture by inhibition of focal adhesion kinase.Stem cell research & therapy · 2020Article
- A 3D culture platform enables development of zinc-binding prodrugs for targeted proliferation of β cells.Science advances · 2020Article
- Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors.Frontiers in bioengineering and biotechnology · 2020Review
- The challenge of correctly reporting hormones content and secretion in isolated human islets.Molecular metabolism · 2019Review
- Advances in islet encapsulation technologies.Nature reviews. Drug discovery · 2017Review
- Mimicking Neuroligin-2 Functions in β-Cells by Functionalized Nanoparticles as a Novel Approach for Antidiabetic Therapy.ACS applied materials & interfaces · 2017Article
- PI3 kinases p110α and PI3K-C2β negatively regulate cAMP via PDE3/8 to control insulin secretion in mouse and human islets.Molecular metabolism · 2016Article
- Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity.Cell death & disease · 2015Article
- An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes.Endocrinology · 2015Article
- Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets.Journal of cellular and molecular medicine · 2015Article
- Compliant 3D microenvironment improves β-cell cluster insulin expression through mechanosensing and β-catenin signaling.Tissue engineering. Part A · 2014Article
- Endodermal differentiation of human pluripotent stem cells to insulin-producing cells in 3D culture.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisBeta cells situated in the islet of Langerhans respond more vigorously to glucose than do dissociated beta cells. Mechanisms for this discrepancy were studied by comparing insulin-producing MIN6 cells aggregated into pseudoislets with MIN6 monolayer cells and mouse and human islets.
methodsMIN6 monolayers, pseudoislets and mouse and human islets were exposed to glucose, α-ketoisocaproic acid (KIC), pyruvate, KIC plus glutamine and the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin. Insulin secretion (ELISA), cytoplasmic Ca(2+) concentration ([Ca(2+)]c; microfluorometry), glucose oxidation (radiolabelling), the expression of genes involved in mitochondrial metabolism (PCR) and the phosphorylation of insulin receptor signalling proteins (western blotting) were measured.
resultsInsulin secretory responses to glucose, pyruvate, KIC and glutamine were higher in pseudoislets than monolayers and comparable to those of human islets. Glucose oxidation and genes for mitochondrial metabolism were upregulated in pseudoislets compared with single cells and monolayers, respectively. Phosphorylation at the inhibitory S636/639 site of IRS-1 was significantly higher in monolayers and dispersed human and mouse cells than pseudoislets and intact human and mouse islets. PI3K inhibition only slightly attenuated glucose-stimulated insulin secretion from monolayers, but substantially reduced that from pseudoislets and human and mouse islets without suppressing the glucose-induced [Ca(2+)]c response. CONCLUSIONS/
interpretationWe propose that islet architecture is critical for proper beta cell mitochondrial metabolism and IRS-1 signalling, and that PI3K regulates insulin secretion at a step distal to the elevation of [Ca(2+)]c.
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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 OpenQuestion graph.