Cited by 272Peroxisome Proliferator-Activated ReceptorsLipid metabolism and disordersLipid metabolism and biosynthesis

The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

Open access
Longuet, Christine, Sinclair, Elaine M., Maida, Adriano, Baggio, Laurie L., Maziarz, Marlena, Charron, Maureen J., Drucker, Daniel J.·2008·Cell Metabolism

Abstract

Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARalpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2008.09.008

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Activation of the glucagon receptor may have a favorable effect on the development and treatment of MAFLD, commonly seen in T2DM.

    “Based on these findings, activation of the glucagon receptor may have a favorable effect on the development and treatment of MAFLD, commonly seen in T2DM.”

    From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [66]

    The Discussion (page not available) reports that glucagon-receptor signaling enhances fatty-acid oxidation and that receptor-deficient mice rapidly develop hepatic steatosis after high-fat feeding. This supports a possible protective role against fatty liver, but the paper does not establish that receptor activation prevents or treats MAFLD in people with T2DM; it also notes that reducing receptor activity lowered liver triglycerides in some diabetic rodents. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • In addition to its blood glucose-increasing effect, glucagon activates fat breakdown and inhibits lipogenesis in the liver, reducing concentrations of non-esterified fatty acids and triacylglycerol, and moderating triglyceride content in liver cells in animal experiments.

    “In addition to its blood glucose-increasing effect, glucagon activates fat breakdown and inhibits lipogenesis in the liver, reducing concentrations of non-esterified fatty acids and triacylglycerol, and moderating triglyceride content in liver cells in animal experiments [66].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Longuet, C., Sinclair, E. M., Maida, A., Baggio, L. L., Maziarz, M., Charron, M. J., & Drucker, D. J.
Affiliations
  • Mount Sinai Hospital (CA)
  • Albert Einstein College of Medicine (US)
Corresponding author
Drucker, Daniel J.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2008-11
Volume
8
Issue
5
Pages
359-371
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2085330452
Cited by
272
References
47
Citations by year
2026: 14 · 2025: 16 · 2024: 23 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 20 · 2016: 10 · 2015: 19 · 2014: 18 · 2013: 12 · 2012: 20
FWCI
3.98
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Canadian Institutes of Health Research (10903)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047425, R01DK47425)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
glucagon receptor, fasting, hepatic lipid metabolism, fatty acid oxidation, hepatic triglyceride secretion, triglyceride synthesis, PPARα, glucagon, hepatic glucose production
MeSH terms
Adaptation, Biological, Animals, Cells, Cultured, Fasting, Fatty Acids, Female, Glucagon, Male, Oxidation-Reduction, RNA, Messenger, Triglycerides, Receptors, Glucagon, Mice, Knockout, Hepatocytes, PPAR alpha, p38 Mitogen-Activated Protein Kinases, Lipid Metabolism, Mice, AMP-Activated Protein Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review