Evidence map›Paper›PMID 26508837›Full record

ArticleDrug design, development and therapy2015

Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals.

Ho-Shan Niu, Po-Ming Ku, Chiang-Shan Niu, Juei-Tang Cheng, Kung-Shing Lee

Open access · goldAbstract read
In one paragraph

Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.2field-weighted citation impact, top 43% 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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

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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

5 authors at 3 institutions in 2 countries.

Ho-Shan NiuDepartment of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
Po-Ming KuDepartment of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan ; Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.
Chiang-Shan NiuDepartment of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
Juei-Tang ChengDepartment of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan ; Institute of Medical Sciences, Chang Jung Christian University, Guiren, Tainan City, Taiwan.
Kung-Shing LeeDepartment of Surgery, Division of Neurosurgery, Pingtung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan ; Department of Surgery, Kaohsiung Medical University, Kaohsiung City, Taiwan ; School of Medicine, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Chi Mei Medical Center · TWTzu Chi College of Technology · TWPingtung Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe development of new drugs for the treatment of diabetes mellitus (DM) is critically important. Insulin resistance (IR) is one of the main problems associated with type-2 DM (T2DM) seen in clinics. GW0742, a selective peroxisome proliferator-activated receptor (PPAR)-δ agonist, has been shown to ameliorate metabolic abnormalities including IR in skeletal muscle in mice fed high-fructose corn syrup. However, the influence of GW0742 on systemic insulin sensitivity has still not been elucidated. Therefore, it is important to investigate the effect of GW0742 on systemic IR in diabetic rats for the development of new drugs.

methodsThe present study used a T2DM animal model to compare the effect of GW0742 on IR using homeostasis model assessment-IR (HOMA-IR) and hyperinsulinemic euglycemic clamping. Additionally, the insulinotropic action of GW0742 was investigated in type-1 DM (T1DM) rats. Changes in the protein expression of glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and in liver, respectively, were also identified by Western blots.

resultsGW0742 attenuated the increased HOMA-IR in diabetic rats fed a fructose-rich diet. This action was blocked by GSK0660 at the dose sufficient to inhibit PPAR-δ. Improvement of IR by GW0742 was also characterized in diabetic rats using hyperinsulinemic euglycemic clamping. Additionally, an increase of insulin sensitivity due to GW0742 was observed in these diabetic rats. Moreover, GW0742 reduced the hyperglycemia in T1DM rats lacking insulin. Western blotting analysis indicated that GW0742 reversed the decrease in GLUT4 and markedly reduced the increased PEPCK in liver.

conclusionThe data showed that GW0742 has the ability to improve glucose homeostasis in diabetic rats through activation of PPAR-δ. Therefore, PPAR-δ is a good target for the development of antidiabetic drugs in the future.

Indexed as

AnimalsBiomarkersBlood GlucoseDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Dose-Response Relationship, DrugDrug DiscoveryFructoseGlucose Transporter Type 4HomeostasisHypoglycemic AgentsInsulinInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiver(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acidBiomarkersBlood GlucoseFructoseGlucose Transporter Type 4Hypoglycemic AgentsInsulinIntracellular Signaling Peptides and ProteinsPck1 protein, ratPhenolsPhosphoenolpyruvate Carboxykinase (GTP)PPAR alphaSlc2a4 protein, ratStreptozocinSulfhydryl CompoundsThiazolesfructose-rich chowHOMA-IRinsulinotropic actioninsulin resistanceratsstreptozotocin

Identifiers

PMID26508837
PMCPMC4610778
OpenAlexW2164898818

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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.