ArticleExperimental cell research2011
Dual mode of glucagon receptor internalization: role of PKCα, GRKs and β-arrestins.
Article in Experimental cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Determinants of plasma levels of proglucagon and the metabolic impact of glucagon receptor signalling: a UK Biobank study.Diabetologia · 2024Article
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Glucagon and Its Receptors in the Mammalian Heart.International journal of molecular sciences · 2023Review
- Article
- Emerging Targets in Type 2 Diabetes and Diabetic Complications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Caveolin-1 Regulates Cellular Metabolism: A Potential Therapeutic Target in Kidney Disease.Frontiers in pharmacology · 2021Review
- Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.The Journal of biological chemistry · 2020Article
- Autophagy mediates hepatic GRK2 degradation to facilitate glucagon-induced metabolic adaptation to fasting.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Mathematical modeling of the glucagon challenge test.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Metabolic regulation through the endosomal system.Traffic (Copenhagen, Denmark) · 2019Review
- Glucagon Receptor Signaling and Glucagon Resistance.International journal of molecular sciences · 2019Review
- Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin.Scientific reports · 2019Article
- GRK5 functions as an oncogenic factor in non-small-cell lung cancer.Cell death & disease · 2018Article
- RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling.Endocrinology · 2017Article
- Association between genetic variants and characteristic symptoms of type 2 diabetes: A matched case-control study.Chinese journal of integrative medicine · 2017Article
- Dual role of GRK5 in cancer development and progression.Translational medicine @ UniSa · 2016Article
- Functional consequences of glucagon-like peptide-1 receptor cross-talk and trafficking.The Journal of biological chemistry · 2015Article
- Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor.Molecules (Basel, Switzerland) · 2014Article
- A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.Diabetes · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Glucagon levels are elevated in diabetes and some liver diseases. Increased glucagon secretion leads to abnormal stimulation of glucagon receptors (GRs) and consequent elevated glucose production in the liver. Blocking glucagon receptor signaling has been proposed as a potential treatment option for diabetes and other conditions associated with hyperglycemia. Elucidating mechanisms of GR desensitization and downregulation may help identify new drug targets besides GR itself. The present study explores the mechanisms of GR internalization and the role of PKCα, GPCR kinases (GRKs) and β-arrestins therein. We have reported previously that PKCα mediates GR phosphorylation and desensitization. While the PKC agonist, PMA, did not affect GR internalization when tested alone, it increased glucagon-mediated GR internalization by 25-40% in GR-expressing HEK-293 cells (HEK-GR cells). In both primary hepatocytes and HEK-GR cells, glucagon treatment recruited PKCα to the plasma membrane where it colocalized with GR. We also observed that overexpression of GRK2, GRK3, or GRK5 enhanced GR internalization. In addition, we found that GR utilizes both clathrin- and caveolin-mediated endocytosis in HEK-GR cells. Glucagon triggered translocation of both β-arrestin1 and β-arrestin2 from the cytosol to the perimembrane region, and overexpression of β-arrestin1 and β-arrestin2 increased GR internalization. Furthermore, both β-arrestin1 and β-arrestin2 colocalized with GR and with Cav-1, suggesting the possible involvement of these arrestins in GR internalization.
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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.