Evidence map›Paper›PMID 26763290›Full record

ArticleCirculation. Heart failure2016

Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice.

Shelley L Baumgardt, Mark Paterson, Thorsten M Leucker, Juan Fang, David X Zhang, Zeljko J Bosnjak, David C Warltier, Judy R Kersten, Zhi-Dong Ge

Abstract read
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In one paragraph

Article in Circulation. Heart failure, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 57 citations in OpenAlex.

  1. Omics-based integrative analysis of sepsis-induced myocardial dysfunction.The Journal of international medical research · 2025
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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

9 authors at 1 institution in 1 country.

Shelley L BaumgardtFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Mark PatersonFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Thorsten M LeuckerFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Juan FangFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
David X ZhangFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Zeljko J BosnjakFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
David C WarltierFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Judy R KerstenFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
Zhi-Dong GeFrom the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.). Wilson.ge99@gmail.com.
Johns Hopkins University · US

Funding

Stem Cell CoreP01GM066730 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI DASH, RANJAN K · 2003 to 2019
$23.6M
TRP Channels In The Regulation of Vascular ToneR01HL096647 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI ZHANG, DAVID X. · 2011 to 2024
$5.5M
Effects of Anesthetics on Ischemic MyocardiumR01HL054820 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI WARLTIER, DAVID C. · 1995 to 2007
$3.1M
MECHANISMS OF MYOCARDIAL ISCHEMIC INJURY IN DIABETESR01HL063705 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI KERSTEN, JUDY R. · 2001 to 2010
$3.0M
NHLBI NIH HHS HL 063705NHLBI NIH HHS R01 HL054820NHLBI NIH HHS R01 HL063705NHLBI NIH HHS R01 HL096647NIGMS NIH HHS GM 066730NIGMS NIH HHS P01 GM066730
6 · The paper itself

Abstract

backgroundDiabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known. The present study examined the effects of SEP and L-Cit on diabetic cardiomyopathy and ischemia/reperfusion injury in obese type 2 diabetic mice. METHODS AND

resultsDb/db and C57BLKS/J mice at 6 to 8 weeks of age received vehicle, SEP, or L-Cit orally alone or in combination for 8 weeks. Cardiac function was evaluated with echocardiography. Db/db mice displayed hyperglycemia, obesity, and normal blood pressure and cardiac function compared with C57BLKS/J mice at 6 to 8 weeks of age. After vehicle treatment for 8 weeks, db/db mice had reduced ejection fraction, mitral E/A ratio, endothelium-dependent relaxation of coronary arteries, tetrahydrobiopterin concentrations, ratio of endothelial nitric oxide synthase dimers/monomers, and nitric oxide levels compared with vehicle-treated C57BLKS/J mice. These detrimental effects of diabetes mellitus were abrogated by co-administration of SEP and L-Cit. Myocardial infarct size was increased, and coronary flow rate and ± dP/dt were decreased during reperfusion in vehicle-treated db/db mice subjected to ischemia/reperfusion injury compared with control mice. Co-administration of SEP and L-Cit decreased infarct size and improved coronary flow rate and cardiac function in both C57BLKS/J and db/db mice.

conclusionsCo-administration of SEP and L-Cit limits diabetic cardiomyopathy and ischemia/reperfusion injury in db/db mice through a tetrahydrobiopterin/endothelial nitric oxide synthase/nitric oxide pathway.

Indexed as

Age FactorsAnimalsBiopterinsCardiotonic AgentsCells, CulturedCitrullineCoronary CirculationCoronary VesselsDiabetes Mellitus, Type 2Diabetic CardiomyopathiesDisease Models, AnimalDrug Administration ScheduleDrug Therapy, CombinationEndothelial CellsIsolated Heart PreparationMice, Inbred C57BLBiopterinsCardiotonic AgentsCitrullineNitric OxideNitric Oxide Synthase Type IIINos3 protein, mousePterinssapropterinsepiapterindiabetic cardiomyopathyischemia reperfusion injurynitric oxide synthasetetrahydrobiopterintype 2 diabetes mellitus

Identifiers

PMID26763290
PMCPMC4714787
OpenAlexW2235908095

What OpenQuestion holds

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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.