ReviewPhysiology (Bethesda, Md.)2019
Hepatic Insulin Clearance: Mechanism and Physiology.
Review in Physiology (Bethesda, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 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
151 citing papers in PubMed, 235 citations in OpenAlex.
- Trial
- The Effect of Various Degrees of Renal or Hepatic Impairment on the Pharmacokinetic Properties of Once-Weekly Insulin Icodec.Clinical pharmacokinetics · 2024Trial
- Acute Insulin Secretory Effects of a Classic Ketogenic Meal in Healthy Subjects: A Randomized Cross-Over Study.Nutrients · 2023Trial
- Postprandial Responses to a Standardised Meal in Hypertension: The Mediatory Role of Visceral Fat Mass.Nutrients · 2022Trial
- Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes.Cell metabolism · 2022Trial
- β Cell function and plasma insulin clearance in people with obesity and different glycemic status.The Journal of clinical investigation · 2022Trial
- Glycemic control improvement in individuals with type 2 diabetes with vitamin KEuropean journal of nutrition · 2021Trial
- Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross-over randomized trial.Journal of diabetes investigation · 2021Trial
- Factors associated with resolution of type-2 diabetes mellitus after sleeve gastrectomy in obese adults.Scientific reports · 2021Trial
- Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics.The Journal of clinical investigation · 2020Trial
- Article
- Differential Pathophysiological Drivers of Susceptibility to Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: Ethnic Differences in Insulin Dynamics, Whole-Body Fat Metabolism, and Organ-Specific Lipid Deposition.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- Bioengineered Exosome-Loaded Immunomodulatory Bioadhesive Spray Reverses Liver Fibrosis and Metabolic Dysfunction That Triggers Beneficial Gut-Liver Crosstalk in Chronic Fatty Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association of Serum Lithium Levels with Insulin Resistance in Type-2 Diabetes Patients.Biological trace element research · 2026Article
- Review
- Strategies to overcome hepatic clearance of endogenous proteins - molecular and formulation approaches.RSC chemical biology · 2026Review
- Failure of Hepatic Insulin Clearance via CEACAM1-Mediated Endocytosis: The Missing Physiological Link Between Proinsulin Misfolding, Hyperinsulinemia, and Metabolic Complications in Type 2 Diabetes, Obesity, and NAFLD.Problemy endokrinologii · 2026Review
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Hepatogenous diabetes in the era of precision medicine: diagnosis, management, and future directions.Clinical and experimental medicine · 2026Review
91 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
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Upon its secretion from pancreatic β-cells, insulin reaches the liver through the portal circulation to exert its action and eventually undergo clearance in the hepatocytes. In addition to insulin secretion, hepatic insulin clearance regulates the homeostatic level of insulin that is required to reach peripheral insulin target tissues to elicit proper insulin action. Receptor-mediated insulin uptake followed by its degradation constitutes the basic mechanism of insulin clearance. Upon its phosphorylation by the insulin receptor tyrosine kinase, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) takes part in the insulin-insulin receptor complex to increase the rate of its endocytosis and targeting to the degradation pathways. This review summarizes how this process is regulated and how it is associated with insulin-degrading enzyme in the liver. It also discusses the physiological implications of impaired hepatic insulin clearance: Whereas reduced insulin clearance cooperates with increased insulin secretion to compensate for insulin resistance, it can also cause hepatic insulin resistance. Because chronic hyperinsulinemia stimulates hepatic de novo lipogenesis, impaired insulin clearance also causes hepatic steatosis. Thus impaired insulin clearance can underlie the link between hepatic insulin resistance and hepatic steatosis. Delineating these regulatory pathways should lead to building more effective therapeutic strategies against metabolic syndrome.
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What Socratic 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 Socratic graph.