ArticleMolecular biology of the cell2015
Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- GIV/Girdin and Exo70 Collaboratively Regulate the Mammalian Polarized Exocytic Machinery.iScience · 2020Article
- Mechanisms of Insulin Action and Insulin Resistance.Physiological reviews · 2018Review
- Membrane Recruitment of the Non-receptor Protein GIV/Girdin (Gα-interacting, Vesicle-associated Protein/Girdin) Is Sufficient for Activating Heterotrimeric G Protein Signaling.The Journal of biological chemistry · 2016Article
- Biochemical, Biophysical and Cellular Techniques to Study the Guanine Nucleotide Exchange Factor, GIV/Girdin.Current protocols in chemical biology · 2016Article
- Article
- Prognostic impact of total and tyrosine phosphorylated GIV/Girdin in breast cancers.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Heterotrimeric G protein signaling via GIV/Girdin: Breaking the rules of engagement, space, and time.BioEssays : news and reviews in molecular, cellular and developmental biology · 2016Review
- The untapped potential of tyrosine-based G protein signaling.Pharmacological research · 2016Review
- GIV/girdin binds exocyst subunit-Exo70 and regulates exocytosis of GLUT4 storage vesicles.Biochemical and biophysical research communicationsArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Gαi, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as a key hub in the immediate postreceptor level, which coordinately enhances the metabolic insulin response and glucose uptake in myotubes via its GEF function. Site-directed mutagenesis or phosphoinhibition of GIV-GEF by the fatty acid/protein kinase C-theta pathway triggers IR. Insulin sensitizers reverse phosphoinhibition of GIV and reinstate insulin sensitivity. We also provide evidence for such reversible regulation of GIV-GEF in skeletal muscles from patients with IR. Thus GIV is an essential upstream component that couples InsR to G-protein signaling to enhance the metabolic insulin response, and impairment of such coupling triggers IR. We also provide evidence that GIV-GEF serves as therapeutic target for exogenous manipulation of physiological insulin response and reversal of IR in skeletal muscles.
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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.