Evidence map›Paper›PMID 26546129›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β.

Agata Jurczyk, Anetta Nowosielska, Natalia Przewozniak, Ken-Edwin Aryee, Philip DiIorio, David Blodgett, Chaoxing Yang, Martha Campbell-Thompson, Mark Atkinson, Leonard Shultz and 4 more

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

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
2.7field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus.The international journal of neuropsychopharmacology · 2021
    Review
  8. Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  9. Co-shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019
    Review
  10. 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

14 authors at 2 institutions in 1 country.

Agata Jurczyk*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Anetta Nowosielska*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Natalia Przewozniak*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Ken-Edwin Aryee*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Philip DiIorio*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
David Blodgett*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Chaoxing Yang*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Martha Campbell-Thompson*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Mark Atkinson*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Leonard Shultz*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Ann Rittenhouse*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
David Harlan*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Dale Greiner*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA.
Rita Bortell*Diabetes Center of Excellence, Program in Molecular Medicine, and Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA; Department of Pathology, University of Florida, Gainesville, Florida, USA; and The Jackson Laboratory; Bar Harbor, Maine, USA rita.bortell@umassmed.edu.
University of Massachusetts Chan Medical School · USUniversity of Massachusetts Amherst · US

Funding

Molecular Mechanisms of Human and Murine Beta Cell Proliferation and RegenerationU01DK089572 · NIDDK · VANDERBILT UNIVERSITY · PI GREINER, DALE LESLIE, HARLAN, DAVID MARSHALL · 2010 to 2014
$8.4M
NIDDK NIH HHS U01 DK089572
6 · The paper itself

Abstract

Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18-30 vs. 1.2-6.3%), independent of body mass index and antipsychotic medication, suggesting shared genetic components may contribute to both diseases. The cause of this association remains unknown. Mutations in disrupted in schizophrenia 1 (DISC1) increase the risk of developing psychiatric disorders [logarithm (base 10) of odds = 7.1]. Here, we identified DISC1 as a major player controlling pancreatic β-cell proliferation and insulin secretion via regulation of glycogen synthase kinase-3β (GSK3β). DISC1 expression was enriched in developing mouse and human pancreas and adult β- and ductal cells. Loss of DISC1 function, through siRNA-mediated depletion or expression of a dominant-negative truncation that models the chromosomal translocation of human DISC1 in schizophrenia, resulted in decreased β-cell proliferation (3 vs. 1%; P < 0.01), increased apoptosis (0.1 vs. 0.6%; P < 0.01), and glucose intolerance in transgenic mice. Insulin secretion was reduced (0.5 vs. 0.1 ng/ml; P < 0.05), and critical β-cell transcription factors Pdx1 and Nkx6.1 were significantly decreased. Impaired DISC1 allowed inappropriate activation of GSK3β in β cells, and antagonizing GSK3β (SB216763; IC50 = 34.3 nM) rescued the β-cell defects. These results uncover an unexpected role for DISC1 in normal β-cell physiology and suggest that DISC1 dysregulation contributes to T2D independently of its importance for cognition.

Indexed as

Cell ProliferationAnimalsDiabetes Mellitus, Type 2Gene Expression RegulationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansInsulin-Secreting CellsMiceMice, TransgenicNerve Tissue ProteinsSchizophreniaTranslocation, GeneticDISC1 protein, humanDisc1 protein, mouseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseNerve Tissue ProteinsdiabetesinsulinsecretionT2D

Identifiers

PMID26546129
PMCPMC4714549
OpenAlexW2113866629

What OpenQuestion 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 OpenQuestion graph.