Evidence map›Paper›PMID 26943366›Full record

ArticleEndocrinology2016

Islet Hypersensitivity to Glucose Is Associated With Disrupted Oscillations and Increased Impact of Proinflammatory Cytokines in Islets From Diabetes-Prone Male Mice.

Kathryn L Corbin, Christopher D Waters, Brett K Shaffer, Gretchen M Verrilli, Craig S Nunemaker

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

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  14. Cytokine-mediated changes in KScientific reports · 2018
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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 at 2 institutions in 1 country.

Kathryn L CorbinDepartment of Biomedical Sciences (K.L.C., C.S.N.), Heritage College of Osteopathic Medicine, and Diabetes Institute (K.L.C., C.S.N.), Ohio University, Athens, Ohio 45701; and Departments of Medicine (C.D.W., B.K.S., G.M.V.) and Biomedical Engineering (C.D.W.), University of Virginia, Charlottesville, Virginia 22908.
Christopher D WatersDepartment of Biomedical Sciences (K.L.C., C.S.N.), Heritage College of Osteopathic Medicine, and Diabetes Institute (K.L.C., C.S.N.), Ohio University, Athens, Ohio 45701; and Departments of Medicine (C.D.W., B.K.S., G.M.V.) and Biomedical Engineering (C.D.W.), University of Virginia, Charlottesville, Virginia 22908.
Brett K ShafferDepartment of Biomedical Sciences (K.L.C., C.S.N.), Heritage College of Osteopathic Medicine, and Diabetes Institute (K.L.C., C.S.N.), Ohio University, Athens, Ohio 45701; and Departments of Medicine (C.D.W., B.K.S., G.M.V.) and Biomedical Engineering (C.D.W.), University of Virginia, Charlottesville, Virginia 22908.
Gretchen M VerrilliDepartment of Biomedical Sciences (K.L.C., C.S.N.), Heritage College of Osteopathic Medicine, and Diabetes Institute (K.L.C., C.S.N.), Ohio University, Athens, Ohio 45701; and Departments of Medicine (C.D.W., B.K.S., G.M.V.) and Biomedical Engineering (C.D.W.), University of Virginia, Charlottesville, Virginia 22908.
Craig S NunemakerDepartment of Biomedical Sciences (K.L.C., C.S.N.), Heritage College of Osteopathic Medicine, and Diabetes Institute (K.L.C., C.S.N.), Ohio University, Athens, Ohio 45701; and Departments of Medicine (C.D.W., B.K.S., G.M.V.) and Biomedical Engineering (C.D.W.), University of Virginia, Charlottesville, Virginia 22908.
University of Virginia · USOhio University · US

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Low-grade Inflammation, Cytokines, and Beta-Cell Dysfunction in Type 2 DiabetesR01DK089182 · NIDDK · UNIVERSITY OF VIRGINIA · PI NUNEMAKER, CRAIG S · 2011 to 2015
$1.6M
NIDDK NIH HHS R01 DK089182NIDDK NIH HHS U24 DK076169
6 · The paper itself

Abstract

Pulsatile insulin release is the primary means of blood glucose regulation. The loss of pulsatility is thought to be an early marker and possible factor in developing type 2 diabetes. Another early adaptation in islet function to compensate for obesity is increased glucose sensitivity (left shift) associated with increased basal insulin release. We provide evidence that oscillatory disruptions may be linked with overcompensation (glucose hypersensitivity) in islets from diabetes-prone mice. We isolated islets from male 4- to 5-week-old (prediabetic) and 10- to 12-week-old (diabetic) leptin-receptor-deficient (db/db) mice and age-matched heterozygous controls. After an overnight incubation in media with 11 mM glucose, we measured islet intracellular calcium in 5, 8, 11, or 15 mM glucose. Islets from heterozygous 10- to 12-week-old mice were quiescent in 5 mM glucose and displayed oscillations with increasing amplitude and/or duration in 8, 11, and 15 mM glucose, respectively. Islets from diabetic 10- to 12-week-old mice, in contrast, showed robust oscillations in 5 mM glucose that declined with increasing glucose. Similar trends were observed at 4-5-weeks of age. A progressive left shift in maximal insulin release was also observed in islets as db/db mice aged. Reducing glucokinase activity with 1 mM D-mannoheptulose restored oscillations in 11 mM glucose. Finally, overnight low-dose cytokine exposure negatively impacted oscillations preferentially in high glucose in diabetic islets compared with heterozygous controls. Our findings suggest the following: 1) islets from frankly diabetic mice can produce oscillations, 2) elevated sensitivity to glucose prevents diabetic mouse islets from producing oscillations in normal postprandial (11-15 mM glucose) conditions, and 3) hypersensitivity to glucose may magnify stress effects from inflammation or other sources.

Indexed as

AnimalsCalciumCalcium SignalingCytokinesDiabetes Mellitus, Type 2GlucoseInsulinInsulin SecretionIslets of LangerhansMaleMiceReceptors, LeptinCalciumCytokinesGlucoseInsulinReceptors, Leptin

Identifiers

PMID26943366
PMCPMC4870867
OpenAlexW2291530750

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.