Evidence map›Paper›PMID 30830873›Full record

ArticleJCI insight2019

Targeting insulin to the liver corrects defects in glucose metabolism caused by peripheral insulin delivery.

Dale S Edgerton, Melanie Scott, Ben Farmer, Phillip E Williams, Peter Madsen, Thomas Kjeldsen, Christian L Brand, Christian Fledelius, Erica Nishimura, Alan D Cherrington

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Insulin Therapy for the Management of Diabetes Mellitus: A Narrative Review of Innovative Treatment Strategies.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Dale S EdgertonVanderbilt University School of Medicine, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.
Melanie ScottVanderbilt University School of Medicine, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.
Ben FarmerVanderbilt University School of Medicine, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.
Phillip E WilliamsVanderbilt University Medical Center, Division of Surgical Research, Nashville, Tennessee, USA.
Peter MadsenResearch and Development, Novo Nordisk A/S, Novo Nordisk Park, Maaleov, Denmark.
Thomas KjeldsenResearch and Development, Novo Nordisk A/S, Novo Nordisk Park, Maaleov, Denmark.
Christian L BrandResearch and Development, Novo Nordisk A/S, Novo Nordisk Park, Maaleov, Denmark.
Christian FledeliusResearch and Development, Novo Nordisk A/S, Novo Nordisk Park, Maaleov, Denmark.
Erica NishimuraResearch and Development, Novo Nordisk A/S, Novo Nordisk Park, Maaleov, Denmark.
Alan D CherringtonVanderbilt University School of Medicine, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.
Novo Nordisk (Denmark) · DKVanderbilt University · USVanderbilt University Medical Center · US

Funding

Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI ELASY, TOM A · 1986 to 2011
$28.1M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
GLUCONEOGENESIS &GLYCOGENOLYSIS:ROLE &REGULATIONR01DK018243 · NIDDK · VANDERBILT UNIVERSITY · PI Alan D Cherrington, Dale S Edgerton · 1986 to 2026
$12.2M
Vanderbilt Mouse Metabolic Phenotyping CenterU2CDK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2016 to 2021
$6.3M
GLUCONEOGENESIS AND GLYCOGENOLYSIS--ROLE OF REGULATIONR37DK018243 · NIDDK · VANDERBILT UNIVERSITY · PI CHERRINGTON, ALAN D · 1998 to 2007
$5.2M
Gluconeogenesis and Glycogenolysis - Role and RegulationR56DK018243 · NIDDK · VANDERBILT UNIVERSITY · PI CHERRINGTON, ALAN D, EDGERTON, DALE S · 2017 to 2017
$236k
NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P60 DK020593NIDDK NIH HHS R01 DK018243NIDDK NIH HHS R37 DK018243NIDDK NIH HHS R56 DK018243NIDDK NIH HHS U24 DK059637NIDDK NIH HHS U2C DK059637
6 · The paper itself

Abstract

Peripheral hyperinsulinemia resulting from subcutaneous insulin injection is associated with metabolic defects which include abnormal glucose metabolism. The first aim of this study was to quantify the impairments in liver and muscle glucose metabolism that occur when insulin is delivered via a peripheral vein compared to when it is given through its endogenous secretory route (the hepatic portal vein) in overnight fasted conscious dogs. The second aim was to determine if peripheral delivery of a hepato-preferential insulin analog could restore the physiologic response to insulin that occurs under meal feeding conditions. This study is the first to show that hepatic glucose uptake correlates with insulin's direct effects on the liver under hyperinsulinemic-hyperglycemic conditions. In addition, glucose uptake was equally divided between the liver and muscle when insulin was infused into the portal vein, but when it was delivered into a peripheral vein the percentage of glucose taken up by muscle was 4-times greater than that going to the liver, with liver glucose uptake being less than half of normal. These defects could not be corrected by adjusting the dose of peripheral insulin. On the other hand, hepatic and non-hepatic glucose metabolism could be fully normalized by a hepato-preferential insulin analog.

Indexed as

Portal VeinAnimalsDogsGlucoseGlucose Clamp TechniqueHindlimbHyperglycemiaHyperinsulinismHypoglycemic AgentsInsulinLiverMuscle, SkeletalVeinsGlucoseHypoglycemic AgentsInsulinDiabetesEndocrinologyGlucose metabolismInsulinMetabolism

Identifiers

PMID30830873
PMCPMC6483654
OpenAlexW2915730620

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.