ArticleThe Journal of clinical investigation2018
Hepatic Gi signaling regulates whole-body glucose homeostasis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 43 citations in OpenAlex.
- Altered GScience advances · 2026Article
- GNature communications · 2024Article
- Identification of GαScientific reports · 2024Article
- Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice.Molecular metabolism · 2024Article
- Distinct physiological characteristics and altered glucagon signaling in GHRH knockout mice: Implications for longevity.Aging cell · 2023Article
- 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
- G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis.Nature communications · 2022Article
- Hepatocyte cholesterol content modulates glucagon receptor signalling.Molecular metabolism · 2022Article
- Insights into the Role of Glucagon Receptor Signaling in Metabolic Regulation from Pharmacological Inhibition and Tissue-Specific Knockout Models.Biomedicines · 2022Review
- In Vivo Metabolic Roles of G Proteins of the Gi Family Studied With Novel Mouse Models.Endocrinology · 2022Review
- Adenosine ABiochemical pharmacology · 2021Article
- Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.Molecular metabolism · 2021Article
- Chemogenetic approaches to identify metabolically important GPCR signaling pathways: Therapeutic implications.Journal of neurochemistry · 2021Review
- G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment.World journal of gastroenterology · 2021Review
- Effect of Gegen Qinlian Decoction on Hepatic Gluconeogenesis in ZDF Rats with Type 2 Diabetes Mellitus Based on the FarnesolEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Designer GPCRs as Novel Tools to Identify Metabolically Important Signaling Pathways.Frontiers in endocrinology · 2021Article
- Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes-Potential Applications for Diabetes and NAFLD.Biomolecules · 2020Review
- Adipocyte GNature communications · 2020Article
- β-arrestin-1 suppresses myogenic reprogramming of brown fat to maintain euglycemia.Science advances · 2020Article
- Adipocyte Gs but not Gi signaling regulates whole-body glucose homeostasis.Molecular metabolism · 2019Article
Corrections and comments
- Commented on by
Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis. Moreover, increased Gi signaling stimulated glucose release in human hepatocytes. A lack of functional Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. Additionally, we delineated a signaling cascade that links hepatic Gi signaling to ROS production, JNK activation, and a subsequent increase in HGP. Taken together, our data support the concept that drugs able to block hepatic Gi-coupled GPCRs may prove beneficial as antidiabetic drugs.
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.