ArticleDiabetologia2013
The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 89 citations in OpenAlex.
- Calcium and TRPML-Mediated Autophagy: Implications in Cancer, Cardiovascular Diseases, and Cardio-Oncology.Cardiovascular toxicology · 2026Review
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes.iScience · 2025Article
- Article
- Whole Exome Sequencing in 26 Saudi Patients Expands the Mutational and Clinical Spectrum of Diabetic Nephropathy.Medicina (Kaunas, Lithuania) · 2025Article
- Targeting macrophages and ion homeostasis in T2D: new genes and therapeutic pathways identified.Frontiers in immunology · 2025Article
- The L-type calcium channel CaV1.3: A potential target for cancer therapy.Journal of cellular and molecular medicine · 2024Review
- Association Study ofInternational journal of molecular sciences · 2024Article
- Sex-dependent intra-islet structural rearrangements affecting alpha-to-beta cell interactions lead to adaptive enhancements of CaDiabetologia · 2024Article
- Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.Pharmacogenomics and personalized medicine · 2024Article
- Identification and validation of diagnostic genes associated with neutrophil extracellular traps of type 2 diabetes mellitus.Frontiers in genetics · 2024Article
- The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice.JCI insight · 2023Article
- Gated Calcium Ion Channel and Mutation Mechanisms in Multidrug-Resistant Tuberculosis.International journal of molecular sciences · 2023Review
- CaBritish journal of pharmacology · 2023Review
- Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.PLoS genetics · 2023Article
- The Association between the Differential Expression of lncRNA and Type 2 Diabetes Mellitus in People with Hypertriglyceridemia.International journal of molecular sciences · 2023Article
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- CACNA1D-Related Channelopathies: From Hypertension to Autism.Handbook of experimental pharmacology · 2023Review
- The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from β cells.Science advances · 2022Article
- Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency.Communications biology · 2022Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisVoltage-gated calcium channels of the L-type have been shown to be essential for rodent pancreatic beta cell function, but data about their presence and regulation in humans are incomplete. We therefore sought to elucidate which L-type channel isoform is functionally important and its association with inherited diabetes-related phenotypes.
methodsBeta cells of human islets from cadaver donors were enriched using FACS to study the expression of the genes encoding voltage-gated calcium channel (Cav)1.2 and Cav1.3 by absolute quantitative PCR in whole human and rat islets, as well as in clonal cells. Single-cell exocytosis was monitored as increases in cell capacitance after treatment with small interfering (si)RNA against CACNA1D (which encodes Cav1.3). Three single nucleotide polymorphisms (SNPs) were genotyped in 8,987 non-diabetic and 2,830 type 2 diabetic individuals from Finland and Sweden and analysed for associations with type 2 diabetes and insulin phenotypes.
resultsIn FACS-enriched human beta cells, CACNA1D mRNA expression exceeded that of CACNA1C (which encodes Cav1.2) by approximately 60-fold and was decreased in islets from type 2 diabetes patients. The latter coincided with diminished secretion of insulin in vitro. CACNA1D siRNA reduced glucose-stimulated insulin release in INS-1 832/13 cells and exocytosis in human beta cells. Phenotype/genotype associations of three SNPs in the CACNA1D gene revealed an association between the C allele of the SNP rs312480 and reduced mRNA expression, as well as decreased insulin secretion in vivo, whereas both rs312486/G and rs9841978/G were associated with type 2 diabetes. CONCLUSION/
interpretationWe conclude that the L-type calcium channel Cav1.3 is important in human glucose-induced insulin secretion, and common variants in CACNA1D might contribute to type 2 diabetes.
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