ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The trial behind it
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Striatal spinophilin enhances dopamine D2 receptor (D2R) interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression.The Journal of pharmacology and experimental therapeutics · 2026Article
- Striatal spinophilin enhances D2R interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.American journal of physiology. Endocrinology and metabolism · 2024Article
- Mechanisms of spinophilin-dependent pancreas dysregulation underlying diabesity.bioRxiv : the preprint server for biology · 2023Article
- Deletion of Spinophilin Promotes White Adipocyte Browning.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The association between RGS4 and choline in cardiac fibrosis.Cell communication and signaling : CCS · 2021Article
- Spinophilin-deficient mice are protected from diet-induced obesity and insulin resistance.American journal of physiology. Endocrinology and metabolism · 2020Article
- The association of spinophilin with disks large-associated protein 3 (SAPAP3) is regulated by metabotropic glutamate receptor (mGluR) 5.Molecular and cellular neurosciences · 2018Article
- The cell biology of the thyroid-disrupting mechanism of dichlorodiphenyltrichloroethane (DDT).Journal of endocrinological investigation · 2018Review
- Regulator of G-protein signaling Gβ5-R7 is a crucial activator of muscarinic M3 receptor-stimulated insulin secretion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Hepatic β-arrestin 2 is essential for maintaining euglycemia.The Journal of clinical investigation · 2017Article
- Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity.The Journal of biological chemistry · 2016Article
- Governing effect of regulatory proteins for Cl(-)/HCO3(-) exchanger 2 activity.Channels (Austin, Tex.) · 2016Article
- Minireview: Role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Minireview: Novel aspects of M3 muscarinic receptor signaling in pancreatic β-cells.Molecular endocrinology (Baltimore, Md.) · 2013Review
- Estimation of the receptor-state affinity constants of ligands in functional studies using wild type and constitutively active mutant receptors: Implications for estimation of agonist bias.Journal of pharmacological and toxicological methodsArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Spinophilin (SPL), a multidomain scaffolding protein known to modulate the activity of different G-protein-coupled receptors, regulates various central nervous system (CNS) functions. However, little is known about the role of SPL expressed in peripheral cell types including pancreatic β cells. In this study, we examined the ability of SPL to modulate the activity of β-cell M(3) muscarinic acetylcholine receptors (M3Rs), which play an important role in facilitating insulin release and maintaining normal blood glucose levels. We demonstrated, by using both in vitro and in vivo approaches (mouse insulinoma cells and SPL-deficient mice), that SPL is a potent negative regulator of M3R-mediated signaling and insulin release. Additional biochemical and biophysical studies, including the use of bioluminescence resonance energy transfer technology, suggested that SPL is able to recruit regulator of G-protein signaling 4 (RGS4) to the M3R signaling complex in an agonist-dependent fashion. Since RGS4 is a member of the RGS family of proteins that act to reduce the lifetime of activated G proteins, these findings support the concept that the inhibitory effects of SPL on M3R activity are mediated by RGS4. These data suggest that SPL or other G-protein-coupled receptor-associated proteins may serve as novel targets for drug therapy aimed at improving β-cell function for the treatment of 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 Socratic graph.