Evidence map›Paper›PMID 29650351›Full record

ArticleMolecular metabolism2018

Overexpression of ST5, an activator of Ras, has no effect on β-cell proliferation in adult mice.

Kristy Ou, Jia Zhang, Yang Jiao, Zhao V Wang, Phillipp Scherer, Klaus H Kaestner

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

6 authors at 3 institutions in 1 country.

Kristy OuDepartment of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: kristyou@pennmedicine.upenn.edu.
Jia ZhangDepartment of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: zhangjia@pennmedicine.upenn.edu.
Yang JiaoDepartment of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Zhao V WangTouchstone Diabetes Center, University of Texas Southwestern, Dallas, TX, 75390, USA.
Phillipp SchererTouchstone Diabetes Center, University of Texas Southwestern, Dallas, TX, 75390, USA. Electronic address: philipp.scherer@utsouthwestern.edu.
Klaus H KaestnerDepartment of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: kaestner@pennmedicine.upenn.edu.
University of Pennsylvania · USSouthwestern Medical Center · USThe University of Texas Southwestern Medical Center · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
Regulation and function of the MEG3 locus in human beta-cellsR01DK088383 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2010 to 2018
$4.8M
Epigenetic Rejuvenation of Human Beta-CellsUC4DK104119 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GLASER, BENJAMIN, KAESTNER, KLAUS H · 2014 to 2014
$3.6M
NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK088383NIDDK NIH HHS UC4 DK104119
6 · The paper itself

Abstract

objectiveBoth Type I and Type II diabetes mellitus result from insufficient functional β-cell mass. Efforts to increase β-cell proliferation as a means to restore β-cell mass have been met with limited success. Suppression of Tumorigenicity 5 (ST5) activates Ras/Erk signaling in the presence of Epidermal Growth Factor (EGF). In the pancreatic islet, Ras/Erk signaling is required for augmented β-cell proliferation during pregnancy, suggesting that ST5 is an appealing candidate to enhance adult β-cell proliferation. We aimed to test the hypothesis that overexpression of ST5 drives adult β-cell proliferation.

methodsWe utilized a doxycycline-inducible bitransgenic mouse model to activate β-cell-specific expression of human ST5 in adult mice at will. Islet morphology, β-cell proliferation, and β-cell mass in control and ST5-overexpressing (ST5 OE) animals were analyzed by immunofluorescent staining, under basal and two stimulated metabolic states: pregnancy and streptozotocin (STZ)-induced β-cell loss.

resultsDoxycycline treatment resulted in robust ST5 overexpression in islets from 12-16 week-old ST5 OE animals compared to controls, without affecting the islet morphology and identity of the β-cells. Under both basal and metabolically stimulated pregnancy states, β-cell proliferation and mass were comparable in ST5 OE and control animals. Furthermore, there was no detectable difference in β-cell proliferation between ST5 OE and control animals in response to STZ-induced β-cell loss.

conclusionsWe successfully derived an inducible bitransgenic mouse model to overexpress ST5 specifically in β-cells. However, our findings demonstrate that ST5 overexpression by itself has no mitogenic effect on the adult β-cell under basal and metabolically challenged states.

Indexed as

Cell ProliferationUp-RegulationAnimalsDiabetes Mellitus, ExperimentalDNA-Binding ProteinsFemaleInsulin-Secreting CellsMaleMiceMice, Inbred C57BLSignal TransductionTumor Suppressor ProteinsDNA-Binding ProteinsSt5 protein, mouseTumor Suppressor ProteinsDiabetesRas/ERK signalingST5 (Suppression Of Tumorigenicity 5)β-cell proliferation

Identifiers

PMID29650351
PMCPMC6001393
OpenAlexW2793678338

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.