| Title |
Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals
|
|---|---|
| Published in |
Drug Design, Development and Therapy, October 2015
|
| DOI | 10.2147/dddt.s95045 |
| Pubmed ID | |
| Authors |
Ho-Shan Niu, Po-Ming Ku, Chiang-Shan Niu, Juei-Tang Cheng, Kung-Shing Lee |
| Abstract |
The 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. The 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. GW0742 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. The 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. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Papua New Guinea | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Unknown | 28 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 21% |
| Student > Bachelor | 5 | 17% |
| Student > Ph. D. Student | 3 | 10% |
| Student > Postgraduate | 2 | 7% |
| Other | 2 | 7% |
| Other | 4 | 14% |
| Unknown | 7 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 24% |
| Medicine and Dentistry | 5 | 17% |
| Agricultural and Biological Sciences | 4 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
| Nursing and Health Professions | 1 | 3% |
| Other | 2 | 7% |
| Unknown | 7 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 October 2023.
All research outputs
#6,967,150
of 25,482,409 outputs
Outputs from Drug Design, Development and Therapy
#441
of 2,273 outputs
Outputs of similar age
#77,381
of 287,110 outputs
Outputs of similar age from Drug Design, Development and Therapy
#16
of 110 outputs
Altmetric has tracked 25,482,409 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 2,273 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done well, scoring higher than 80% of its peers.
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We're also able to compare this research output to 110 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.