ArticleScientific reports2016
Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Hepatic GPR75 exacerbates MASH through GNAI2-dependent signaling.Hepatology (Baltimore, Md.) · 2026Article
- Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).Experimental and therapeutic medicine · 2026Review
- Synergistic regulation of selenium yeast and vitamin E on the rumen microbiota-VFA-liver axis in lambs.BMC microbiology · 2026Article
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.Signal transduction and targeted therapy · 2025Article
- Does Incretin Agonism Have Sustainable Efficacy?Cells · 2024Review
- Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.Journal of diabetes investigation · 2024Article
- Article
- Inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine AAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Sleeve gastrectomy causes weight-loss independent improvements in hepatic steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
- Network-level analysis of ageing and its relationship with diseases and tissue regeneration in the mouse liver.Scientific reports · 2023Article
- Effect of Quercetin Nanoparticles on Hepatic and Intestinal Enzymes and Stress-Related Genes in Nile Tilapia Fish Exposed to Silver Nanoparticles.Biomedicines · 2023Article
- Excessive gluconeogenesis causes the hepatic insulin resistance paradox and its sequelae.Heliyon · 2022Review
- PIDDosome-SCAP crosstalk controls high-fructose-diet-dependent transition from simple steatosis to steatohepatitis.Cell metabolism · 2022Article
- Review
- Multi-organ Coordination of Lipoprotein Secretion by Hormones, Nutrients and Neural Networks.Endocrine reviews · 2021Review
- CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions.Nutrients · 2021Review
- Vitamin E treatment in NAFLD patients demonstrates that oxidative stress drives steatosis through upregulation of de-novo lipogenesis.Redox biology · 2020Article
- Transcription factors activated through RIP (regulated intramembrane proteolysis) and RAT (regulated alternative translocation).The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia.
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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.