Evidence map›Paper›PMID 24703698›Full record

ArticleCell metabolism2014

Glucagon regulates hepatic kisspeptin to impair insulin secretion.

Woo-Jin Song, Prosenjit Mondal, Andrew Wolfe, Laura C Alonso, Rachel Stamateris, Benny W T Ong, Owen C Lim, Kil S Yang, Sally Radovick, Horacio J Novaira and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 1 pooled it
23.9field-weighted citation impact, top 1% 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

115 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.

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  17. The identification of novel missense variant inOpen medicine (Warsaw, Poland) · 2025
    Article
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55 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 1 country.

Woo-Jin SongMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Prosenjit MondalMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Andrew WolfeDivision of Pediatric Endocrinology, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Physiology, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Laura C AlonsoDiabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Rachel StamaterisDiabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Benny W T OngMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Owen C LimMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Kil S YangMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Sally RadovickDivision of Pediatric Endocrinology, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Horacio J NovairaDivision of Pediatric Endocrinology, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA.
Emily A FarberCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Charles R FarberCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Stephen D TurnerDepartment of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Mehboob A HussainMetabolism Division, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Diabetes Institute, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Medicine, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Pediatrics, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA; Department of Biological Chemistry, Johns Hopkins University, CMSC Building 10-113, Baltimore, MD, 21287, USA. Electronic address: mhussai4@jhmi.edu.
Johns Hopkins University · USUniversity of Virginia · USUniversity of Massachusetts Chan Medical School · US

Funding

Murine Mutagenesis CoreP30NS050274 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOLODKIN, ALEX L · 2005 to 2020
$10.9M
JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BRANCATI, FREDERICK L · 2013 to 2017
$9.7M
Diabetes Research and Training CenterP60DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI WONDISFORD, FREDRIC E. · 2008 to 2012
$9.1M
Sex Steroids, Kisspeptin and Regulation of GnRHR01HD068777 · NICHD · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI HOFFMAN, GLORIA E, LEVINE, JON E · 2012 to 2016
$2.4M
Beta-cell ProliferationR01DK081472 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HUSSAIN, MEHBOOB A, WONDISFORD, FREDRIC E. · 2009 to 2013
$2.1M
Hepatic endocrine suppression of the pancreatic beta-cellR01DK101591 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUSSAIN, MEHBOOB A, WOLFE, ANDREW M · 2014 to 2017
$2.0M
Free Fatty Acids, p16 and Pancreatic Beta Cell ProliferationR01DK095140 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ALONSO, LAURA C · 2012 to 2016
$1.9M
Discovery of Bone Formation Genes through Integrative GenomicsR01AR057759 · NIAMS · UNIVERSITY OF VIRGINIA · PI FARBER, CHARLES R · 2011 to 2015
$1.7M
1/2 Kisspeptin Regulation and GPR54 Signaling in ReproductionU01HD066432 · NICHD · JOHNS HOPKINS UNIVERSITY · PI HOFFMAN, GLORIA E, WOLFE, ANDREW M · 2010 to 2014
$1.6M
CONTROL OF CELL SPECIFIC EXPRESSION OF THE GNRH GENEF32HD008222 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI WOLFE, ANDREW M · 1997 to 1999
–
NIAMS NIH HHS R01 AR057759NICHD NIH HHS F32 HD008222NICHD NIH HHS R01 HD068777NICHD NIH HHS U01 HD066432NIDDK NIH HHS P30 DK079637NIDDK NIH HHS P60 DK079637NIDDK NIH HHS R01 DK081472NIDDK NIH HHS R01 DK095140NIDDK NIH HHS R01 DK101591NINDS NIH HHS P30 NS050274
6 · The paper itself

Abstract

Early in the pathogenesis of type 2 diabetes mellitus (T2DM), dysregulated glucagon secretion from pancreatic α cells occurs prior to impaired glucose-stimulated insulin secretion (GSIS) from β cells. However, whether hyperglucagonemia is causally linked to β cell dysfunction remains unclear. Here we show that glucagon stimulates via cAMP-PKA-CREB signaling hepatic production of the neuropeptide kisspeptin1, which acts on β cells to suppress GSIS. Synthetic kisspeptin suppresses GSIS in vivo in mice and from isolated islets in a kisspeptin1 receptor-dependent manner. Kisspeptin1 is increased in livers and in serum from humans with T2DM and from mouse models of diabetes mellitus. Importantly, liver Kiss1 knockdown in hyperglucagonemic, glucose-intolerant, high-fat-diet fed, and Lepr(db/db) mice augments GSIS and improves glucose tolerance. These observations indicate a hormonal circuit between the liver and the endocrine pancreas in glycemia regulation and suggest in T2DM a sequential link between hyperglucagonemia via hepatic kisspeptin1 to impaired insulin secretion.

Indexed as

AnimalsGene Expression RegulationGene Knockdown TechniquesGlucagonGluconeogenesisImmunohistochemistryInsulinInsulin SecretionKisspeptinsLiverLuciferasesMiceMice, Inbred NODModels, BiologicalGlucagonInsulinKiss1 protein, mouseKisspeptinsLuciferases

Identifiers

PMID24703698
PMCPMC4058888
OpenAlexW2004507900

What OpenQuestion 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 OpenQuestion graph.