Evidence map›Paper›PMID 21822931›Full record

ArticleDiabetologia2011

Homozygous carriers of the G allele of rs4664447 of the glucagon gene (GCG) are characterised by decreased fasting and stimulated levels of insulin, glucagon and glucagon-like peptide (GLP)-1.

S S Torekov, L Ma, N Grarup, B Hartmann, I A Hainerová, U Kielgast, H Kissow, M Rosenkilde, GIANT Consortium, J Lebl and 11 more

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Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists.The Journal of clinical endocrinology and metabolism · 2020
    Review
  4. Article
  5. Reduced GLP-1 response to a meal is associated with theCentral-European journal of immunology · 2019
    Article
  6. Article
  7. Article
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

21 authors at 8 institutions in 3 countries.

S S TorekovDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Torekov@sund.ku.dk
L Ma
N Grarup
B Hartmann
I A Hainerová
U Kielgast
H Kissow
M Rosenkilde
GIANT Consortium
J Lebl
D R Witte
T Jørgensen
A Sandbaek
T Lauritzen
O D Madsen
J Wang
A Linneberg
S Madsbad
J J Holst
T Hansen
O Pedersen
University of Copenhagen · DKNovo Nordisk Foundation · DKAarhus University · DKBGI Group (China) · CNCharles University · CZGlostrup Hospital · DKHvidovre Hospital · DKSteno Diabetes Center · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisThe glucagon gene (GCG) encodes several hormones important for energy metabolism: glucagon, oxyntomodulin and glucagon-like peptide (GLP)-1 and -2. Variants in GCG may associate with type 2 diabetes, obesity and/or related metabolic traits.

methodsGCG was re-sequenced as a candidate gene in 865 European individuals. Twenty-nine variants were identified. Four variants that were considered to have a likelihood for altered functionality: rs4664447, rs7581952, Ile158Val and Trp169Ter, were genotyped in 17,584 Danes.

resultsWhen examined in 5,760 treatment-naive individuals, homozygous carriers of the low frequency (minor allele frequency 2.3%) G allele of rs4664447, predicted to disrupt an essential splice enhancer binding site, had lower levels of fasting plasma glucose (mean ± SD, 4.8 ± 1.2 vs 5.5 ± 0.8 mmol/l, p = 0.004); fasting serum insulin (22 ± 14 vs 42 ± 27 pmol/l, p = 0.04); glucose-stimulated serum insulin (159 ± 83 vs 290 ± 183 pmol/l, p = 0.01) and adult height (165 ± 10 vs 172 ± 9 cm, p = 0.0009) compared with A allele carriers. During oral glucose tolerance and hyperglycaemic arginine stimulation tests, the plasma AUC for GLP-1 (730 ± 69 vs 1,334 ± 288 pmol/l × min, p = 0.0002) and basal and stimulated levels of serum insulin and plasma glucagon were ∼50% decreased (p < 0.001) among three homozygous carriers compared with nine matched wild-type carriers. rs7581952, Ile158Val and Trp169Ter (where 'Ter' indicates 'termination') variants of GCG did not significantly associate or co-segregate with the metabolic traits examined. CONCLUSIONS/

interpretationRe-sequencing of GCG revealed a low frequency intronic variant, rs4664447, and follow-up physiological studies suggest that this variant in homozygous form may cause decreased fasting and stimulated levels of insulin, glucagon and GLP-1. Overall, our findings suggest that variation in GCG has no major impact on carbohydrate metabolism in the study populations examined.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAgedAge of OnsetCase-Control StudiesChildChild, PreschoolCzechoslovakiaDenmarkDiabetes Mellitus, Type 2EuropeFemaleGenetic Association StudiesGlucagonGlucagon-Like Peptide 1GlucagonGlucagon-Like Peptide 1Insulin

Identifiers

PMID21822931
OpenAlexW2094664516

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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.