ArticleAmerican journal of physiology. Endocrinology and metabolism2009
A highly energetic process couples calcium influx through L-type calcium channels to insulin secretion in pancreatic beta-cells.
Article in American journal of physiology. Endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Pooled it
- Efficacy of vitamin D supplementation on glycemic control in type 2 diabetes patients: A meta-analysis of interventional studies.Medicine · 2019Pooled it
- The Amount of Releasable Insulin Depends on Continuous Oxidative Phosphorylation.Function (Oxford, England) · 2025Article
- The Proton Leak of the Inner Mitochondrial Membrane Is Enlarged in Freshly Isolated Pancreatic Islets.Biomedicines · 2024Article
- Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion.Frontiers in endocrinology · 2024Article
- A peptide triple agonist of GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors promotes glycemic control and weight loss.Scientific reports · 2023Article
- Effect of vitamin D supplementation on type 2 diabetes biomarkers: an umbrella of interventional meta-analyses.Diabetology & metabolic syndrome · 2023Review
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- Fluidics system for resolving concentration-dependent effects of dissolved gases on tissue metabolism.eLife · 2021Article
- Review
- Synthesis, Optimization, and Biological Evaluation of Corrinated Conjugates of the GLP-1R Agonist Exendin-4.Journal of medicinal chemistry · 2021Article
- Glucolipotoxicity and GLP-1 secretion.BMJ open diabetes research & care · 2021Article
- Design and Evaluation of Peptide Dual-Agonists of GLP-1 and NPY2 Receptors for Glucoregulation and Weight Loss with Mitigated Nausea and Emesis.Journal of medicinal chemistry · 2021Article
- Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes.Frontiers in immunology · 2021Review
- Tumor-like features of gene expression and metabolic profiles in enlarged pancreatic islets are associated with impaired incretin-induced insulin secretion in obese diabetes: A study of Zucker fatty diabetes mellitus rat.Journal of diabetes investigation · 2020Article
- Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet.PloS one · 2020Article
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
- Article
- Article
- A method for high-throughput functional imaging of single cells within heterogeneous cell preparations.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Calcium (Ca(2+)) influx is required for the sustained secretion of insulin and is accompanied by a large rate of energy usage. We hypothesize that the energy usage reflects a process [Ca(2+)/metabolic coupling process (CMCP)] that couples Ca(2+) to insulin secretion by pancreatic islets. The aim of the study was to test this hypothesis by testing the effect of inhibiting candidate Ca(2+)-sensitive proteins proposed to play a critical role in the CMCP. The effects of the inhibitors on oxygen consumption rate (OCR), a reflection of ATP usage, and insulin secretion rate (ISR) were compared with those seen when L-type Ca(2+) channels were blocked with nimodipine. We reasoned that if a downstream Ca(2+)-regulated site was responsible for the OCR associated with the CMCP, then its inhibition should mimic the effect of nimodipine. Consistent with previous findings, nimodipine decreased glucose-stimulated OCR by 36% and cytosolic Ca(2+) by 46% and completely suppressed ISR in rat pancreatic islets. Inhibitors of three calmodulin-sensitive proteins (myosin light-chain kinase, calcineurin, and Ca(2+)/calmodulin-dependent protein kinase II) did not meet the criteria. In contrast, KN-62 severed the connection between Ca(2+) influx, OCR, and ISR without interfering with Ca(2+) influx. In the presence of nimodipine or KN-62, potentiators of ISR, acetylcholine, GLP-1, and arginine had little effect on insulin secretion, suggesting that the CMCP is also essential for the amplification of ISR. In conclusion, a KN-62-sensitive process directly mediates the effects of Ca(2+) influx via L-type Ca(2+) channels on OCR and ISR, supporting the essential role of the CMCP in mediating ISR.
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