ReviewAmerican journal of physiology. Cell physiology2012
Evolving insights regarding mechanisms for the inhibition of insulin release by norepinephrine and heterotrimeric G proteins.
Review in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 79 citations in OpenAlex.
- Increased adrenergic signaling is responsible for decreased glucose-stimulated insulin secretion in the chronically hyperinsulinemic ovine fetus.Endocrinology · 2015Trial
- Chromogranin A and catestatin regulate pancreatic islet homeostasis, endocrine function, and neurotransmitter signaling.Communications biology · 2025Article
- iGlucoSnFR2: A genetically encoded fluorescent sensor for measuring intracellular or extracellular glucose in vivo in mouse brain.Science advances · 2025Article
- Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review.International journal of molecular sciences · 2025Review
- β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.Pharmacology research & perspectives · 2025Article
- Regulatory Role of Fatty Acid Metabolism on Glucose-Induced Changes in Insulin and Glucagon Secretion by Pancreatic Islet Cells.International journal of molecular sciences · 2024Review
- β-blockers and metabolic modulation: unraveling the complex interplay with glucose metabolism, inflammation and oxidative stress.Frontiers in pharmacology · 2024Review
- 12,13-diHOME and noradrenaline are associated with the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2023Article
- Dual pancreatic adrenergic and dopaminergic signaling as a therapeutic target of bromocriptine.iScience · 2022Article
- Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels KActa physiologica (Oxford, England) · 2022Review
- Tissue-specific responses that constrain glucose oxidation and increase lactate production with the severity of hypoxemia in fetal sheep.American journal of physiology. Endocrinology and metabolism · 2022Article
- Circulating GLP-1 Levels in Patients with Pheochromocytoma/Paraganglioma.International journal of endocrinology · 2022Article
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Pancreatic Islets Exhibit Dysregulated Adaptation of Insulin Secretion after Chronic Epinephrine Exposure.Current issues in molecular biology · 2021Article
- Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.Frontiers in pharmacology · 2021Article
- Neuromedin U uses Gαi2 and Gαo to suppress glucose-stimulated Ca2+ signaling and insulin secretion in pancreatic β cells.PloS one · 2021Article
- A Pilot Study of Perioperative External Circumferential Cryoablation of Human Renal Arteries for Sympathetic Denervation.Vascular specialist international · 2020Article
- Chronically elevated norepinephrine concentrations lower glucose uptake in fetal sheep.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Independent roles of beta-adrenergic and glucocorticoid receptors in systemic and pulmonary effects of ozone.Inhalation toxicology · 2020Article
- αFrontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Norepinephrine has for many years been known to have three major effects on the pancreatic β-cell which lead to the inhibition of insulin release. These are activation of K(+) channels to hyperpolarize the cell and prevent the gating of voltage-dependent Ca(2+) channels that increase intracellular Ca(2+) concentration ([Ca(2+)](i)) and trigger release; inhibition of adenylyl cyclases, thus preventing the augmentation of stimulated insulin release by cyclic AMP; and a "distal" effect that occurs downstream of increased [Ca(2+)](i) to inhibit exocytosis. All three are mediated by the pertussis toxin (PTX)-sensitive heterotrimeric Gi and Go proteins. The distal inhibitory effect on exocytosis is now known to be due to the binding of G protein βγ subunits to the synaptosomal-associated protein of 25 kDa (SNAP-25) on the soluble NSF attachment protein receptor (SNARE) complex. Recent studies have uncovered two more actions of norepinephrine on the β-cell: 1) retardation of the refilling of the readily releasable granule pool after it has been discharged, an action that is mediated by Gαi(1) and/or Gαi(2); and 2) inhibition of endocytosis that is mediated by Gz. Of importance also are new findings that Gαo regulates the number of docked granules in the β-cell, and that Gαo(2) maintains a tonic inhibitory influence on secretion. The latter provides another explanation as to why PTX, which blocks the effect of Gαo(2), was initially called "islet activating protein." Finally, there is clear evidence that overexpression of α(2A)-adrenergic receptors in β-cells can cause type 2 diabetes.
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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.