Evidence map›Paper›PMID 39829839›Full record

ArticlebioRxiv : the preprint server for biology2025

A Microphysiological Model of Progressive Human Hepatic Insulin Resistance.

Dominick J Hellen, Jessica Ungerleider, Erin Tevonian, Pierre Sphabmixay, Priyatanu Roy, Caroline Lewis, Jacob Jeppesen, Damien Demozay, Linda G Griffith

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Dominick J HellenDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.ORCID 0000-0002-2793-399X
Jessica UngerleiderDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.
Erin TevonianDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.ORCID 0000-0001-7645-1957
Pierre SphabmixayDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.ORCID 0000-0003-0119-9173
Priyatanu RoyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.ORCID 0000-0002-7299-9306
Caroline LewisWhitehead Institute for Biomedical Research, Cambridge, MA, 02139 US.ORCID 0000-0003-1787-5084
Jacob JeppesenWhitehead Institute for Biomedical Research, Cambridge, MA, 02139 US.
Damien DemozayLiver Disease, Novo Nordisk A/S, Måløv, Denmark.
Linda G GriffithDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 US.ORCID 0000-0002-1801-5548

Funding

TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
Inflammation in human obesity and type 2 diabetesR01DK108056 · NIDDK · UNIVERSITY OF KENTUCKY · PI LAUFFENBURGER, DOUGLAS A, NIKOLAJCZYK, BARBARA · 2016 to 2019
$2.6M
NIDDK NIH HHS R01 DK108056NIEHS NIH HHS T32 ES007020
6 · The paper itself

Abstract

Background & Aims: Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse Methods: Replicate liver MPS were maintained in media with either 200 pM (normal) or 800 pM (T2D) insulin for up to 3 weeks. Conditions of standard glucose (5.5 mM), hyperglycemia (11 mM glucose), normal (20μM) and elevated FFA (100 μM), alone and in combination were used at each insulin concentration, either continuously or reversing back to standard media after 2 weeks of simulated T2D conditions. Hepatic glucose production, activation of signaling pathways, insulin clearance, transcriptome analysis, and intracellular lipid and bile acid accumulation were assessed. Results: Hyperinsulinemia alone induces insulin resistance after one week of exposure, while hyperglycemia and increased FFAs significantly exacerbate this phenotype. Hyperinsulinemia, along with elevated glucose and FFAs, transcriptionally predisposes hepatocytes to insulin resistance through altered metabolic and immune signaling pathways. The phenotypes observed in hyperinsulinemia and nutrient overload are partially reversible upon return to normophysiologic conditions. Conclusions: Our enhanced

Indexed as

hepatocytesMicrofluidicsnon-alcoholic fatty liver diseasetissue engineeringType 2 diabetes

Identifiers

PMID39829839
PMCPMC11741310

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.