ArticleThe Journal of biological chemistry2015
Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Computational screening of Alternaria metabolites as potential DPP-4 inhibitors: ADMET, molecular docking, molecular dynamics, and network pharmacology analysis.Molecular diversity · 2026Article
- Breaking the Calcium Overload Cycle in Acute Pancreatitis: Emerging Pharmacological Strategies.Digestive diseases and sciences · 2026Review
- Vitamin K as an Endocrine Modulator: Mechanistic Links to Glucose Metabolism and Beyond.Nutrients · 2026Review
- The photoswitchable cannabinoid azo-HU308 enables optical control of CaFEBS open bio · 2026Article
- Article
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Differential Sensitivity of TRPC- and ORAI-Mediated Calcium Entries to 1‑[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl]imidazole Chloride (SKF-96365).ACS pharmacology & translational science · 2025Article
- Normotensive metabolic syndrome in Transient Receptor Potential Canonical Channel type 1 Trpc1-/- mice.Biology open · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Role of TRP Channels in Metabolism-Related Diseases.International journal of molecular sciences · 2024Review
- CaFrontiers in endocrinology · 2024Review
- Article
- Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.International journal of molecular sciences · 2023Review
- Vitamin K-dependent carboxylation regulates CaCell reports · 2023Article
- Light-stimulated insulin secretion from pancreatic islet-like organoids derived from human pluripotent stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Store-operated CaPNAS nexus · 2023Article
- TRPC3 Regulates Islet Beta-Cell Insulin Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- RyR2 regulates store-operated Ca2+ entry, phospholipase C activity, and electrical excitability in the insulinoma cell line INS-1.PloS one · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Store-operated Ca(2+) channels (SOCs) are voltage-independent Ca(2+) channels activated upon depletion of the endoplasmic reticulum Ca(2+) stores. Early studies suggest the contribution of such channels to Ca(2+) homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca(2+) depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca(2+) imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca(2+) entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes.
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