Evidence map›Paper›PMID 15655710›Full record

ArticleHormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells.

G G Holz, G Holz

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

Article in Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 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 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Docosahexaenoic acid has an anti-diabetic effect in streptozotocin-induced diabetic mice.International journal of clinical and experimental medicine · 2014
    Article
  6. Regulation of glucose homeostasis by GLP-1.Progress in molecular biology and translational science · 2014
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. RD Lawrence Lecture 2008: Targeting GLP-1 release as a potential strategy for the therapy of Type 2 diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2008
    Review
  16. Article
  17. Article
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4 · The record

Corrections and comments

  • Erratum issued
    Holz, G [corrected to Holz, GG]
5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

G G HolzDepartment of Physiology and Neuroscience, New York University School of Medicine, NY 10016, USA. holzg01@popmail.med.nyu.edu
G Holz
New York University · US

Funding

Insulinotropin: A Modulator Of B-Cell Glucose SignalingR01DK045817 · NIDDK · UPSTATE MEDICAL UNIVERSITY · PI HOLZ, GEORGE G · 2001 to 2008
$3.0M
NIDDK NIH HHS R01 DK045817NIDDK NIH HHS R01-DK45817
6 · The paper itself

Abstract

The GLP-1 receptor is a Class B heptahelical G-protein-coupled receptor that stimulates cAMP production in pancreatic beta-cells. GLP-1 utilizes this receptor to activate two distinct classes of cAMP-binding proteins: protein kinase A (PKA) and the Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). Actions of GLP-1 mediated by PKA and Epac include the recruitment and priming of secretory granules, thereby increasing the number of granules available for Ca(2+)-dependent exocytosis. Simultaneously, GLP-1 promotes Ca(2+) influx and mobilizes an intracellular source of Ca(2+). GLP-1 sensitizes intracellular Ca(2+) release channels (ryanodine and IP (3) receptors) to stimulatory effects of Ca(2+), thereby promoting Ca(2+)-induced Ca(2+) release (CICR). In the model presented here, CICR activates mitochondrial dehydrogenases, thereby upregulating glucose-dependent production of ATP. The resultant increase in cytosolic [ATP]/[ADP] concentration ratio leads to closure of ATP-sensitive K(+) channels (K-ATP), membrane depolarization, and influx of Ca(2+) through voltage-dependent Ca(2+) channels (VDCCs). Ca(2+) influx stimulates exocytosis of secretory granules by promoting their fusion with the plasma membrane. Under conditions where Ca(2+) release channels are sensitized by GLP-1, Ca(2+) influx also stimulates CICR, generating an additional round of ATP production and K-ATP channel closure. In the absence of glucose, no "fuel" is available to support ATP production, and GLP-1 fails to stimulate insulin secretion. This new "feed-forward" hypothesis of beta-cell stimulus-secretion coupling may provide a mechanistic explanation as to how GLP-1 exerts a beneficial blood glucose-lowering effect in type 2 diabetic subjects.

Indexed as

AnimalsCalciumCyclic AMP-Dependent Protein KinasesGlucagonGlucagon-Like Peptide 1Guanine Nucleotide Exchange FactorsHumansInsulinInsulin SecretionIslets of LangerhansMitochondriaPeptide FragmentsPotassium ChannelsProtein PrecursorsReceptors, GlucagonCalciumCyclic AMP-Dependent Protein KinasesGlucagonGlucagon-Like Peptide 1Guanine Nucleotide Exchange FactorsInsulinPeptide FragmentsPotassium ChannelsProtein PrecursorsRAPGEF3 protein, humanReceptors, Glucagon

Identifiers

PMID15655710
PMCPMC2914250
OpenAlexW2002939114

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.