Evidence map›Paper›PMID 31984442›Full record

ArticleDiabetologia2020

PAM haploinsufficiency does not accelerate the development of diet- and human IAPP-induced diabetes in mice.

Yi-Chun Chen, Richard E Mains, Betty A Eipper, Brad G Hoffman, Traci A Czyzyk, John E Pintar, C Bruce Verchere

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

Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.1field-weighted citation impact, top 8% 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, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Yi-Chun ChenDepartment of Surgery, University of British Columbia and BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.
Richard E MainsDepartment of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
Betty A EipperDepartment of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
Brad G HoffmanDepartment of Surgery, University of British Columbia and BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.
Traci A CzyzykDivision of Cardio-renal and Metabolic Disease, Merck Research Laboratories, San Francisco, CA, USA.
John E PintarDepartment of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
C Bruce VerchereDepartment of Surgery, University of British Columbia and BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. bverchere@bcchr.ca.
BC Children's Hospital · CAUConn Health · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USRutgers, The State University of New Jersey · US

Funding

CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONR01DK032948 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH ANNE, MAINS, RICHARD E · 1986 to 2019
$7.3M
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR01DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH ANNE, KING, STEPHEN M · 1986 to 2017
$6.4M
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR37DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH A · 1989 to 2004
$2.8M
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR56DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH A · 2005 to 2005
$104k
CIHR PJT - 153156Juvenile Diabetes Research Foundation 3-SRA-2014-39-Q-RJuvenile Diabetes Research Foundation International 3-PDF-2017-373-A-NNIDDK NIH HHS R01 DK032948NIDDK NIH HHS R01 DK032949NIDDK NIH HHS R37 DK032949NIDDK NIH HHS R56 DK032949NIH HHS DK-32949
6 · The paper itself

Abstract

aims/hypothesisPeptide hormones are first synthesised as larger, inactive precursors that are converted to their active forms by endopeptidase cleavage and post-translational modifications, such as amidation. Recent, large-scale genome-wide studies have suggested that two coding variants of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), are associated with impaired insulin secretion and increased type 2 diabetes risk. We aimed to elucidate the role of PAM in modulating beta cell peptide amidation, beta cell function and the development of diabetes.

methodsPAM transcript and protein levels were analysed in mouse islets following induction of endoplasmic reticulum (ER) or cytokine stress, and PAM expression patterns were examined in human islets. To study whether haploinsufficiency of PAM accelerates the development of diabetes, Pam

resultsImmunostaining revealed high expression of PAM in alpha, beta and delta cells in human pancreatic islets. Pam mRNA and PAM protein expression were reduced in mouse islets following administration of an HFD, and in isolated islets following induction of ER stress with thapsigargin, or cytokine stress with IL-1β, IFN-γ and TFN-α. Despite Pam CONCLUSIONS/

interpretationHaploinsufficiency of PAM in mice does not accelerate the development of diet-induced obesity or hIAPP transgene-induced diabetes.

Indexed as

Amidine-LyasesAnimalsCells, CulturedDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Disease ProgressionEpistasis, GeneticFemaleGenetic Predisposition to DiseaseHaploinsufficiencyHumansInsulin-Secreting CellsIslet Amyloid PolypeptideIslets of LangerhansMaleMiceAmidine-LyasesIslet Amyloid PolypeptideMixed Function OxygenasesPAM protein, humanAmidationGlucose homeostasisIAPPInsulin secretionPAM

Identifiers

PMID31984442
PMCPMC7864590
OpenAlexW3003748555

What OpenQuestion holds

Textmetadata
LicenceTDM
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.