Evidence map›Paper›PMID 24705606›Full record

ArticleDiabetologia2014

Doc2b enrichment enhances glucose homeostasis in mice via potentiation of insulin secretion and peripheral insulin sensitivity.

Latha Ramalingam, Eunjin Oh, Debbie C Thurmond

Open access · greenAbstract read
In one paragraph

Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  13. Article
  14. Protecting functional β cells with a therapeutic peptide.Annals of translational medicine · 2018
    Article
  15. Article
  16. Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2018
    Article
  17. Review
  18. Article
  19. Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017
    Review
  20. Review
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

3 authors at 2 institutions in 1 country.

Latha RamalingamDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Eunjin Oh
Debbie C Thurmond
Indiana University School of MedicineIndiana University – Purdue University Indianapolis · US

Funding

Regulation of Glucose Homeostasis by Munc18 ProteinsR01DK067912 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI THURMOND, DEBBIE C · 2004 to 2023
$6.5M
Targeting PAK1 to improve functional beta-cell mass and insulin sensitivityR01DK102233 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI THURMOND, DEBBIE C, VELUTHAKAL, RAJAKRISHNAN · 2014 to 2024
$3.3M
Cdc42-regulated insulin granule exocytosisR01DK076614 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI THURMOND, DEBBIE C · 2008 to 2012
$1.6M
NIDDK NIH HHS DK067912 ANDNIDDK NIH HHS DK076614NIDDK NIH HHS R01 DK067912NIDDK NIH HHS R01 DK076614NIDDK NIH HHS R01 DK102233
6 · The paper itself

Abstract

aims/hypothesisInsulin secretion from pancreatic beta cells and insulin-stimulated glucose uptake into skeletal muscle are processes regulated by similar isoforms of the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) and mammalian homologue of unc-18 (Munc18) protein families. Double C2 domain β (Doc2b), a SNARE- and Munc18-interacting protein, is implicated as a crucial effector of glycaemic control. However, whether Doc2b is naturally limiting for these processes, and whether Doc2b enrichment might exert a beneficial effect upon glycaemia in vivo, remains undetermined.

methodsTetracycline-repressible transgenic (Tg) mice engineered to overexpress Doc2b simultaneously in the pancreas, skeletal muscle and adipose tissues were compared with wild-type (Wt) littermate mice regarding glucose and insulin tolerance, islet function in vivo and ex vivo, and skeletal muscle GLUT4 accumulation in transverse tubule/sarcolemmal surface membranes. SNARE complex formation was further assessed using Doc2b overexpressing L6-GLUT4-myc myoblasts to derive mechanisms relatable to physiological in vivo analyses.

resultsDoc2b Tg mice cleared glucose substantially faster than Wt mice, correlated with enhancements in both phases of insulin secretion and peripheral insulin sensitivity. Heightened peripheral insulin sensitivity correlated with elevated insulin-stimulated GLUT4 vesicle accumulation in cell surface membranes of Doc2b Tg mouse skeletal muscle. Mechanistic studies demonstrated Doc2b enrichment to enhance syntaxin-4-SNARE complex formation in skeletal muscle cells. CONCLUSIONS/

interpretationDoc2b is a limiting factor in SNARE exocytosis events pertinent to glycaemic regulation in vivo. Doc2b enrichment may provide a novel means to simultaneously boost islet and skeletal muscle function in vivo in the treatment and/or prevention of diabetes.

Indexed as

Adipose TissueAnimalsCalcium-Binding ProteinsExocytosisGlucoseHomeostasisInsulinInsulin ResistanceInsulin SecretionMiceMice, TransgenicMuscle, SkeletalNerve Tissue ProteinsPancreasR-SNARE ProteinsCalcium-Binding ProteinsDoc2b protein, mouseGlucoseInsulinNerve Tissue ProteinsR-SNARE Proteins

Identifiers

PMID24705606
PMCPMC4055500
OpenAlexW1976212598

What Socratic 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 Socratic graph.