ArticleThe Journal of clinical investigation2009
Hepatic energy state is regulated by glucagon receptor signaling in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- Hepatic ketogenesis is not required for exercise training to mitigate diet-induced liver steatosis in male mice.Function (Oxford, England) · 2026Article
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Hepatic ketogenesis supports liver lipid homeostasis during acute exercise but is not required for exercise training to mitigate liver steatosis in mice.bioRxiv : the preprint server for biology · 2026Article
- Identification and Regulation of a Hepatic Lipogenic Metabolon.bioRxiv : the preprint server for biology · 2026Article
- What Do We Know of Human Fuel Use during Aerobic Exercise, and How Do We Know It?Physiology (Bethesda, Md.) · 2026Review
- Review
- Fluoxetine and agomelatine mitigate anhedonic and hepatic changes in chronic restraint stress rat model.Scientific reports · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- High glucose affects the cardiac function of diabetic Akita mice by inhibiting cardiac ATP synthase beta subunit.International journal of cardiology. Cardiovascular risk and prevention · 2025Article
- Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism.Cell reports · 2025Article
- PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.Military Medical Research · 2024Article
- Metabolic Fluxes in the Renal Cortex Are Dysregulated In Vivo in Response to High-Fat Diet.Diabetes · 2024Article
- Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.American journal of physiology. Endocrinology and metabolism · 2024Article
- Exercise training adaptations in liver glycogen and glycerolipids require hepatic AMP-activated protein kinase in mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Loss of hepatic phosphoenolpyruvate carboxykinase 1 dysregulates metabolic responses to acute exercise but enhances adaptations to exercise training in mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Important Hormones Regulating Lipid Metabolism.Molecules (Basel, Switzerland) · 2022Review
- The Finnish genetic heritage in 2022 - from diagnosis to translational research.Disease models & mechanisms · 2022Review
- Glucagon, cyclic AMP, and hepatic glucose mobilization: A half-century of uncertainty.Physiological reports · 2022Review
- ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism.Frontiers in physiology · 2022Review
- Multitissue 2H/13C flux analysis reveals reciprocal upregulation of renal gluconeogenesis in hepatic PEPCK-C-knockout mice.JCI insight · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with energy requirements. This coupling is fundamental in the adaptive response to many conditions and is impaired in metabolic disease. We have found that the hepatic energy state is substantially reduced following exercise, fasting, and exposure to other metabolic stressors in C57BL/6 mice. Glucagon receptor signaling was hypothesized to mediate this reduction because increased plasma levels of glucagon are characteristic of metabolic stress and because this hormone stimulates energy consumption linked to increased gluconeogenic flux through cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) and associated pathways. We developed what we believe to be a novel hyperglucagonemic-euglycemic clamp to isolate an increment in glucagon levels while maintaining fasting glucose and insulin. Metabolic stress and a physiological rise in glucagon lowered the hepatic energy state and amplified AMP-activated protein kinase signaling in control mice, but these changes were abolished in glucagon receptor- null mice and mice with liver-specific PEPCK-C deletion. 129X1/Sv mice, which do not mount a glucagon response to hypoglycemia, displayed an increased hepatic energy state compared with C57BL/6 mice in which glucagon was elevated. Taken together, these data demonstrate in vivo that the hepatic energy state is sensitive to glucagon receptor activation and requires PEPCK-C, thus providing new insights into liver metabolism.
Indexed as
Identifiers
What OpenQuestion holds
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.