ArticleThe Journal of clinical investigation2017
Ca2+ channel clustering with insulin-containing granules is disturbed in type 2 diabetes.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- Postnatal refinement of CaChannels (Austin, Tex.) · 2026Article
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- Proteomic analysis of pancreatic endocrine cells by mechanistic single-cell isolation identifies membrane pathways.Experimental & molecular medicine · 2026Article
- MicroRNA-Driven Regulation of β-Cell Function in Type 2 Diabetes: Molecular Mechanisms, Network Insights, and Translational Perspectives.Acta physiologica (Oxford, England) · 2026Review
- One Week Exposure to a Somatostatin Receptor 2 Antagonist (SSTR2a) Enhances Glucagon Counterregulation to Insulin-Induced Hypoglycaemia and Does Not Worsen Glycemia in a Male Rat Model of Insulin-Requiring Type 2 Diabetes.Diabetes, obesity & metabolism · 2026Article
- CaThe Journal of physiology · 2026Article
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex.Communications biology · 2025Article
- Submembrane liprin-α1 clusters spatially localize insulin granule fusion.The Journal of cell biology · 2025Article
- The Amount of Releasable Insulin Depends on Continuous Oxidative Phosphorylation.Function (Oxford, England) · 2025Article
- Dietary formaldehyde: a silent aggravator of diabetes and cognitive impairments.Nutrition & diabetes · 2025Review
- Septin5 deletion enhances β-cell exocytosis by releasing microtubule-tethered insulin granules onto plasma membrane.Nature communications · 2025Article
- Role of the extracellular matrix in amylin aggregation: Opportunities for improved therapy in type 2 diabetes mellitus.Journal of biosciences · 2025Review
- Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes.Journal of extracellular biology · 2024Article
- Changes in Cells Associated with Insulin Resistance.International journal of molecular sciences · 2024Review
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis.Frontiers in endocrinology · 2024Article
- Review
- CaAmerican journal of physiology. Endocrinology and metabolism · 2023Review
- CaBiomedicines · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Loss of first-phase insulin secretion is an early sign of developing type 2 diabetes (T2D). Ca2+ entry through voltage-gated L-type Ca2+ channels triggers exocytosis of insulin-containing granules in pancreatic β cells and is required for the postprandial spike in insulin secretion. Using high-resolution microscopy, we have identified a subset of docked insulin granules in human β cells and rat-derived clonal insulin 1 (INS1) cells for which localized Ca2+ influx triggers exocytosis with high probability and minimal latency. This immediately releasable pool (IRP) of granules, identified both structurally and functionally, was absent in β cells from human T2D donors and in INS1 cells cultured in fatty acids that mimic the diabetic state. Upon arrival at the plasma membrane, IRP granules slowly associated with 15 to 20 L-type channels. We determined that recruitment depended on a direct interaction with the synaptic protein Munc13, because expression of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2 domain all disrupted L-type channel clustering at granules and ablated fast exocytosis. Thus, rapid insulin secretion requires Munc13-mediated recruitment of L-type Ca2+ channels in close proximity to insulin granules. Loss of this organization underlies disturbed insulin secretion kinetics in T2D.
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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.