Evidence map›Paper›PMID 31349033›Full record

ReviewNeurobiology of disease2019

The effects of insulin and insulin-like growth factor I on amyloid precursor protein phosphorylation in in vitro and in vivo models of Alzheimer's disease.

Bhumsoo Kim, Sarah E Elzinga, Rosemary E Henn, Lisa M McGinley, Eva L Feldman

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Review
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  11. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
    Article
  12. Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
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  16. Article
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  19. Article
  20. Extracellular vesicles, the emerging mirrors of brain physiopathology.International journal of biological sciences · 2023
    Review
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

5 authors.

Bhumsoo KimDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, United States of America.
Sarah E ElzingaDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, United States of America.
Rosemary E HennDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, United States of America.
Lisa M McGinleyDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, United States of America.
Eva L FeldmanDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, United States of America. Electronic address: efeldman@umich.edu.

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
Multidisciplinary Training Program in Basic Diabetes ResearchT32DK101357 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETER ARVAN, Ormond A MacDougald · 2014 to 2026
$4.1M
NIDDK NIH HHS T32 DK101357NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a growing problem worldwide, and there are currently no effective treatments for this devastating disease. The neurotrophic growth factors insulin and insulin-like growth factor-I (IGF-I) are currently being investigated as potential therapeutic approaches for AD in preclinical and clinical studies. However, given that the metabolic syndrome (MetS) and diabetes are risk factors for AD, it is unknown how associated insulin resistance (IR) in the brain may impact the effectiveness of these therapies for AD. In this report, we therefore investigated the mechanisms underlying the effects of insulin and IGF-I on AD-associated pathology in the context of IR, with particular emphasis on phosphorylation of amyloid precursor protein (APP), a key step in promoting amyloid plaque formation in AD. Both insulin and IGF-I decreased APP phosphorylation in cultured primary cortical neurons, supporting their therapeutic use in AD. Induction of IR blocked the beneficial effect of insulin and reduced the effect of IGF-I on APP dephosphorylation. These effects were mediated by the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (Akt) pathway, as inhibition of this pathway during IR restored the effect of IGF-I on APP dephosphorylation. Finally, we explored the translational relevance of these results in vivo by demonstrating that high fat diet fed mice, a robust model of IR and MetS, exhibited the expected increased brain APP phosphorylation. Overall, these data suggest that the beneficial therapeutic effect of insulin and IGF-I on APP phosphorylation is negatively impacted by IR, and suggest that insulin and IGF-I alone may not be appropriate therapies for AD patients with IR, MetS, or diabetes.

Indexed as

Disease Models, AnimalAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCells, CulturedCerebral CortexDiet, High-FatInsulinInsulin-Like Growth Factor IInsulin ResistanceMiceMice, Inbred C57BLObesityPhosphorylationRatsRats, Sprague-DawleyAmyloid beta-Protein PrecursorInsulininsulin-like growth factor-1, ratInsulin-Like Growth Factor IAlzheimer's diseaseAmyloid precursor proteinIGF-IInsulinInsulin resistance

Identifiers

PMID31349033
PMCPMC6834902

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Registered trials

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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.