ArticleCirculation research2019
Hepatic Glucagon Signaling Regulates PCSK9 and Low-Density Lipoprotein Cholesterol.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
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
33 citing papers in PubMed, 63 citations in OpenAlex.
- Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.Diabetes, obesity & metabolism · 2025Trial
- Glucagon receptor agonist aggravates a murine model of Balkan nephropathy.American journal of physiology. Renal physiology · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Metabolic, enterohepatic and gut microbial effects of atorvastatin in healthy men.Endocrine connections · 2026Article
- Hepatic GCGR is required for the superior weight loss and metabolic effects of a structurally related analogue of the dual GCGR/GLP-1R agonist survodutide in mice.Diabetes, obesity & metabolism · 2026Article
- Comparative study of palmitoleic acid, sea buckthorn oil, and lovastatin in hepatocellular steatosis model.Scientific reports · 2026Article
- Preoperative LDL-C and mortality after cardiac valve surgery: a retrospective cohort study on the mediating role of inflammatory risk.Lipids in health and disease · 2026Article
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression.Nature communications · 2025Article
- Regulatory mechanisms of hepatocyte PCSK9 expression: translating mechanistic insights into potential nutraceuticals.Chinese medicine · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- PCSK9 promotes progression of anaplastic thyroid cancer through E-cadherin endocytosis.Cell death & disease · 2025Article
- RAP1A suppresses hepatic steatosis by regulating amino acid-mediated mTORC1 activation.JHEP reports : innovation in hepatology · 2025Article
- Glucagon in metabolic disease: a mini-review of emerging multi-organ roles beyond glycemic control.Frontiers in endocrinology · 2025Review
- Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon.Nature communications · 2024Article
- Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.The Journal of endocrinology · 2024Review
- Downregulation of the kidney glucagon receptor, essential for renal function and systemic homeostasis, contributes to chronic kidney disease.Cell metabolism · 2024Article
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- The Regulation and Secretion of Glucagon in Response to Nutrient Composition: Unraveling Their Intricate Mechanisms.Nutrients · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleGlucagon is a key hormone that regulates the adaptive metabolic responses to fasting. In addition to maintaining glucose homeostasis, glucagon participates in the regulation of cholesterol metabolism; however, the molecular pathways underlying this effect are incompletely understood.
objectiveWe sought to determine the role of hepatic Gcgr (glucagon receptor) signaling in plasma cholesterol regulation and identify its underlying molecular mechanisms. METHODS AND
resultsWe show that Gcgr signaling plays an essential role in LDL-C (low-density lipoprotein cholesterol) homeostasis through regulating the PCSK9 (proprotein convertase subtilisin/kexin type 9) levels. Silencing of hepatic Gcgr or inhibition of glucagon action increased hepatic and plasma PCSK9 and resulted in lower LDLR (LDL receptor) protein and increased plasma LDL-C. Conversely, treatment of wild-type (WT) mice with glucagon lowered LDL-C levels, whereas this response was abrogated in Pcsk9
conclusionsThese findings provide novel insights into the molecular interplay between hepatic glucagon signaling and lipid metabolism and describe a new posttranscriptional mechanism of PCSK9 regulation.
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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.