ArticleJCI insight2017
Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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
73 citing papers in PubMed, 121 citations in OpenAlex.
- Reduced hypoglycaemia using liver-targeted insulin in individuals with type 1 diabetes.Diabetes, obesity & metabolism · 2022Trial
- Ultra rapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study.Diabetes, obesity & metabolism · 2020Trial
- Trial
- Acute AKT signaling increases glucose phosphorylation and contribution to glycogen in hepatocytes.iScience · 2026Article
- Regulation and clinical manifestations of gluconeogenesis dysfunction.npj metabolic health and disease · 2026Review
- Metabolic and Signaling Dysregulation in a Cellular Model of Hepatic Insulin Resistance.Current issues in molecular biology · 2026Article
- A novel subset of hepatocytes is simultaneously gluconeogenic andbioRxiv : the preprint server for biology · 2026Article
- Hemoglobin glycation index can be used as a predictor of diabetes mellitus and prediabetes: a cohort study.BMC endocrine disorders · 2025Article
- New insights into the role of metallothioneins in obesity and diabetes.International journal of obesity (2005) · 2025Review
- Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling.Cell metabolism · 2025Article
- Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance.Endocrine reviews · 2025Review
- Regulation of LEAP2 by insulin and glucagon in mice and humans.Cell reports. Medicine · 2025Article
- The deuterated glucose insulin tolerance test: a new tool to delineate insulin-stimulated glucose uptake from suppression of endogenous glucose production.Life metabolism · 2025Article
- Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.Frontiers in endocrinology · 2025Review
- Metabolic and genetic mechanisms of metabolic dysfunction-associated steatotic liver disease: an integrative perspective from molecular pathways to clinical challenges.Frontiers in endocrinology · 2025Review
- Prospects for the convergence of polyphenols with pharmaceutical drugs in type 2 diabetes: Challenges, risks, and strategies.Pharmacological reviews · 2025Review
- Analysis of Exosomal miRNA and Hepatic mRNA Expression in the Dysregulation of Insulin Action in Perimenopausal Mice.Journal of diabetes research · 2025Article
- Analysis of Glucose Responsive Glucagon Therapeutics using Computational Models of the Glucoregulatory System.Advanced healthcare materials · 2024Article
- Morning Engagement of Hepatic Insulin Receptors Improves Afternoon Hepatic Glucose Disposal and Storage.bioRxiv : the preprint server for biology · 2024Article
- Intranasal Insulin Eases Autism in Rats via GDF-15 and Anti-Inflammatory Pathways.Current issues in molecular biology · 2024Article
13 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
9 authors at 1 institution in 1 country.
Funding
Abstract
Insulin can inhibit hepatic glucose production (HGP) by acting directly on the liver as well as indirectly through effects on adipose tissue, pancreas, and brain. While insulin's indirect effects are indisputable, their physiologic role in the suppression of HGP seen in response to increased insulin secretion is not clear. Likewise, the mechanisms by which insulin suppresses lipolysis and pancreatic α cell secretion under physiologic circumstances are also debated. In this study, insulin was infused into the hepatic portal vein to mimic increased insulin secretion, and insulin's indirect liver effects were blocked either individually or collectively. During physiologic hyperinsulinemia, plasma free fatty acid (FFA) and glucagon levels were clamped at basal values and brain insulin action was blocked, but insulin's direct effects on the liver were left intact. Insulin was equally effective at suppressing HGP when its indirect effects were absent as when they were present. In addition, the inhibition of lipolysis, as well as glucagon and insulin secretion, did not require CNS insulin action or decreased plasma FFA. This indicates that the rapid suppression of HGP is attributable to insulin's direct effect on the liver and that its indirect effects are redundant in the context of a physiologic increase in insulin secretion.
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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.