ArticleDiabetes2012
Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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Who cites it
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.Human molecular genetics · 2016Pooled it
- Diabetes-associated genetic variation in TCF7L2 alters pulsatile insulin secretion in humans.JCI insight · 2020Trial
- A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients.Scientific reports · 2016Trial
- Trial
- Molecular Genetics of β-Cell Compensation in Gestational Diabetes Mellitus: Insights from CDKAL1, SLC30A8 and HHEX.International journal of molecular sciences · 2026Review
- Voltage-gated potassium channels as important modulators of glucose-stimulated insulin secretion in pancreatic β-cells: insights from rodent and human studies.Frontiers in endocrinology · 2026Review
- Membrane Merger Dynamics in Exocytosis and Endocytosis.Advances in experimental medicine and biology · 2026Review
- Quantitative analysis of human adult pancreatic histology reveals separate fatty and fibrotic phenotypes in type 2 diabetes.Diabetologia · 2025Article
- Single Fusion Pore Analysis via Single Cell Amperometry Uncovers Impaired Pore Expansion That Restricts Insulin Exocytosis in Human Type 2 Diabetes.Angewandte Chemie (International ed. in English) · 2025Article
- JP-14: A Trace Amine-Associated Receptor 1 Agonist with Anti-Metabolic Disorder Potential.International journal of molecular sciences · 2025Article
- A novel link betweenBiomedical reports · 2025Article
- Stimulus-Secretion Coupling Mechanisms of Glucose-Induced Insulin Secretion: Biochemical Discrepancies Among the Canonical, ADP Privation, and GABA-Shunt Models.International journal of molecular sciences · 2025Review
- Loss of β-Cell KATP Reduces Ca2+ Sensitivity of Insulin Secretion and Trpm5 Expression.Diabetes · 2025Article
- Heritable dysregulation of DNA methylation may underlie the diabetogenic effects of paternal preconception exposure to inorganic arsenic in C57BL/6J mice.Toxicology and applied pharmacology · 2025Article
- Unraveling the pathophysiology of type 2 diabetes with a new selectively bred animal model, the Oikawa-Nagao mouse.Diabetology international · 2025Review
- Teplizumab's immunomodulatory effects on pancreatic β-cell function in type 1 diabetes mellitus.Clinical diabetes and endocrinology · 2024Review
- Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- CaFrontiers in endocrinology · 2024Review
- Modulation of insulin secretion by RBFOX2-mediated alternative splicing.Nature communications · 2023Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 5 institutions in 4 countries.
Funding
Abstract
The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation to genetic risk profiles in diabetic and nondiabetic donors. Islets from donors with T2D exhibited impaired insulin secretion, which was more pronounced in lean than obese diabetic donors. We assessed the impact of 14 disease susceptibility variants on measures of glucose sensing, exocytosis, and structure. Variants near TCF7L2 and ADRA2A were associated with reduced glucose-induced insulin secretion, whereas susceptibility variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoked insulin exocytosis. KCNQ1, ADRA2A, KCNJ11, HHEX/IDE, and SLC2A2 variants affected granule docking. We combined our results to create a novel genetic risk score for β-cell dysfunction that includes aberrant granule docking, decreased Ca(2+) sensitivity of exocytosis, and reduced insulin release. Individuals with a high risk score displayed an impaired response to intravenous glucose and deteriorating insulin secretion over time. Our results underscore the importance of defects in β-cell exocytosis in T2D and demonstrate the potential of cellular phenotypic characterization in the elucidation of complex genetic disorders.
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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.