Evidence map›Paper›PMID 27095270›Full record

ArticleAging cell2016

Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

Mashani Mohamad, Sarah Jayne Mitchell, Lindsay Edward Wu, Melanie Yvonne White, Stuart James Cordwell, John Mach, Samantha Marie Solon-Biet, Dawn Boyer, Dawn Nines, Abhirup Das and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 77 citations in OpenAlex.

  1. Review
  2. Review
  3. Liver, ageing and disease.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Insulin Sensitivity Initially Worsens but Later Improves With Aging in Male C57BL/6N Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Biomarkers of aging.Science China. Life sciences · 2023
    Review
  18. Review
  19. The Roles of Myeloid Cells in Aging-related Liver Diseases.International journal of biological sciences · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 4 countries.

Mashani MohamadAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.
Sarah Jayne MitchellTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Lindsay Edward WuLaboratory for Ageing Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Melanie Yvonne WhiteCharles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Stuart James CordwellCharles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
John MachKolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
Samantha Marie Solon-BietAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.
Dawn BoyerTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Dawn NinesTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Abhirup DasLaboratory for Ageing Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Shi-Yun Catherine LiLaboratory for Ageing Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Alessandra WarrenAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.
Sarah Nicole HilmerKolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
Robin FraserDepartment of Pathology, University of Otago, Christchurch, New Zealand.
David Andrew SinclairLaboratory for Ageing Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Stephen James SimpsonCharles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Rafael de CaboTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
David George Le CouteurAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.
Victoria Carroll CoggerAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.
The University of Sydney · AUUNSW Sydney · AUAnzac Research Institute · AUNational Institute on Aging · USNational Institutes of Health · USRoyal North Shore Hospital · AUUniversiti Teknologi MARA · MYUniversity of Otago · NZ

Funding

Role of Sgs1 DNA helicase in telomere maintenanceR01AG019719 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SINCLAIR, DAVID A. · 2001 to 2022
$5.3M
SIRT1 as a regulator of health and lifespan of mammalsR37AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2012 to 2021
$4.1M
NIA NIH HHS R01 AG019719NIA NIH HHS R37 AG028730
6 · The paper itself

Abstract

While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

Indexed as

Insulin ResistanceMicrocirculationAgingAnimalsDisease Models, AnimalEndothelial CellsGlucoseGlycogenInsulinLiverMaleMice, Inbred C57BLPoloxamerPorosityRats, Inbred F344Staining and LabelingGlucoseGlycogenInsulinPoloxamerageingagingendotheliumfenestraefenestrationshyperinsulinemia

Identifiers

PMID27095270
PMCPMC4933657
OpenAlexW2338708728

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.