Evidence map›Paper›PMID 26409461›Full record

ArticleDiabetologia2015

Deletion of ARNT/HIF1β in pancreatic beta cells does not impair glucose homeostasis in mice, but is associated with defective glucose sensing ex vivo.

Renjitha Pillai, Sabina Paglialunga, Monica Hoang, Katelyn Cousteils, Kacey J Prentice, Eric Bombardier, Mei Huang, Frank J Gonzalez, A Russell Tupling, Michael B Wheeler and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.International journal of molecular sciences · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Integrative Analysis of HNF1B mRNA in Human Cancers Based on Data Mining.International journal of medical sciences · 2020
    Article
  8. Review
  9. 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

11 authors at 3 institutions in 2 countries.

Renjitha PillaiSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5.
Sabina PaglialungaSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5.
Monica HoangSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5.
Katelyn CousteilsSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5.
Kacey J PrenticeDepartment of Physiology, University of Toronto, Toronto, ON, Canada.
Eric BombardierDepartment of Kinesiology, University of Waterloo, Waterloo, ON, Canada.
Mei HuangSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5.
Frank J GonzalezLaboratory of Metabolism, National Cancer Institute, Bethesda, MD, USA.
A Russell TuplingDepartment of Kinesiology, University of Waterloo, Waterloo, ON, Canada.
Michael B WheelerDepartment of Physiology, University of Toronto, Toronto, ON, Canada.
Jamie W JosephSchool of Pharmacy, University of Waterloo, Health Science Campus building A, room 4008, 10A Victoria Street South, Kitchener, ON, Canada, N2G 1C5. j3joseph@uwaterloo.ca.
University of Waterloo · CAUniversity of Toronto · CANational Cancer Institute · US

Funding

Xenobiotic receptorsZIABC005562 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$26.9M
TRANSCRIPTIONAL REGULATION OF GENES ENCODING XENOBIOTIC METABOLIZING ENZYMESZ01BC005561 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK · 1996 to 2008
$754k
CIHR FRN 86638CIHR MOP-324754Intramural NIH HHS Z01 BC005561
6 · The paper itself

Abstract

aims/hypothesisIt has been suggested that the transcription factor ARNT/HIF1β is critical for maintaining in vivo glucose homeostasis and pancreatic beta cell glucose-stimulated insulin secretion (GSIS). Our goal was to gain more insights into the metabolic defects seen after the loss of ARNT/HIF1β in beta cells.

methodsThe in vivo and in vitro consequences of the loss of ARNT/HIF1β were investigated in beta cell specific Arnt/Hif1β knockout mice (β-Arnt (fl/fl/Cre) mice).

resultsThe only in vivo defects found in β-Arnt (fl/fl/Cre) mice were significant increases in the respiratory exchange ratio and in vivo carbohydrate oxidation, and a decrease in lipid oxidation. The mitochondrial oxygen consumption rate was unaltered in mouse β-Arnt (fl/fl/Cre) islets upon glucose stimulation. β-Arnt (fl/fl/Cre) islets had an impairment in the glucose-stimulated increase in Ca(2+) signalling and a reduced insulin secretory response to glucose in the presence of KCl and diazoxide. The glucose-stimulated increase in the NADPH/NADP(+) ratio was reduced in β-Arnt (fl/fl/Cre) islets. The reduced GSIS and NADPH/NADP(+) levels in β-Arnt (fl/fl/Cre) islets could be rescued by treatment with membrane-permeable tricarboxylic acid intermediates. Small interfering (si)RNA mediated knockdown of ARNT/HIF1β in human islets also inhibited GSIS. These results suggest that the regulation of GSIS by the KATP channel-dependent and -independent pathways is affected by the loss of ARNT/HIF1β in islets. CONCLUSIONS/

interpretationThis study provides three new insights into the role of ARNT/HIF1β in beta cells: (1) ARNT/HIF1β deletion in mice impairs GSIS ex vivo; (2) β-Arnt (fl/fl/Cre) mice have an increased respiratory exchange ratio; and (3) ARNT/HIF1β is required for GSIS in human islets.

Indexed as

AnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorGlucoseGlucose Tolerance TestHomeostasisHuman Growth HormoneHumansInsulinInsulin-Secreting CellsInsulin SecretionMembrane Potential, MitochondrialMiceMice, KnockoutNADPOxygen ConsumptionPulmonary Gas ExchangeArnt protein, mouseAryl Hydrocarbon Receptor Nuclear TranslocatorGlucoseHuman Growth HormoneInsulinNADPARNT/HIF1βInsulin releaseMetabolismPancreatic beta cell

Identifiers

PMID26409461
PMCPMC6338330
OpenAlexW2115646936

What OpenQuestion holds

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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.