Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor γ agonist, on insulin resistance in Zucker fatty rat

Minoura, Hideaki; Takeshita, S; Yamamoto, Tadashi; Mabuchi, Miyuki; Hirosumi, Jiro; Takakura, Shoji; Kawamura, Ikuo; Seki, Jiro; Manda, Toshitaka; Ita, Makoto; Mutoh, Seitaro

doi:10.1016/j.ejphar.2005.05.042

Cited by 34 publications

(32 citation statements)

References 19 publications

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“…This agrees with the findings reported by Terrettaz et al (2). YM440 did not change the HGP or GDR in the basal state, which is the same result obtained with other PPARγ agonists (3,6,7,11). Both GDR and HGP in the basal state reflect the tissue sensitivity to the endogenous insulin level.…”

Section: Discussionsupporting

confidence: 92%

“…ZF rats are reportedly used as a model of insulin resistance, presenting symptoms of hyperinsulinemia, hyperlipidemia, moderate hyperglycemia, and marked glucose intolerance. Several groups have used ZF rats to study the ameliorating effects of insulin resistance by insulin sensitizers such as TZDs or non-TZD PPARγ agonists (5,6,10,11).…”

Section: Discussionmentioning

confidence: 99%

“…TZDs appear to function as insulin sensitizers mainly through this nuclear receptor activation (12). Previous studies using the euglycemic-hyperinsulineamic clamp method showed that TZDs (3, 6, 11, 13 -16) and other non-TZD PPARγ agonists (7,10,11) ameliorate both hepatic and peripheral insulin resistance in rat diabetic models.…”

Section: Introductionmentioning

confidence: 99%

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The Novel Hypoglycemic Agent YM440 Improves Hepatic Insulin Resistance in Obese Zucker Fatty Rats

et al. 2006

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Abstract. The novel hypoglycemic agent YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl] phenoxy}but-2-ene) is a ligand of the peroxisome proliferator-activated receptor (PPAR) γ. YM440 has unique pharmacological profiles both in vitro and in vivo, but, it is not clear whether the compound has a significant effect on hepatic or peripheral insulin response throughout the body. The aim of this study is to examine the effects of YM440 on hepatic and peripheral insulin resistance in Zucker fatty (ZF) rats using the euglycemic-hyperinsulinaemic clamp technique. Treatment of ZF rats with YM440 (300 mg / kg per day) for 2 weeks significantly decreased plasma concentrations of glucose and insulin without inducing obesity. YM440 caused a 2-fold increase in the glucose infusion rate during euglycemic clamping compared with the vehicle control. YM440 also decreased the percent change in hepatic glucose production rate caused by intravenous insulin infusion in ZF rats. YM440 had no significant effect on the glucose disposal rate. These results indicate that YM440 ameliorates hepatic, but not peripheral insulin resistance in ZF rats. These findings strongly suggest that the main target organ of YM440 is the liver, unlike other PPARγ agonist.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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The Novel Hypoglycemic Agent YM440 Improves Hepatic Insulin Resistance in Obese Zucker Fatty Rats

et al. 2006

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“…48,49) Insulin resistance is not only associated with hyperinsulinemia and hyperglycemia, but also with such other disorders as atherosclerosis, hypertension, and abnormal lipid profiles which are now collectively referred to as the metabolic syndrome or insulin resistance-associated disorders.…”

Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Phlorotannins from Edible Brown Algae,Ecklonia stoloniferaandEisenia bicyclis

Moon

Islam

Ahn

et al. 2011

Bioscience, Biotechnology, and Biochemistry

137

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“…For example, selective PPARγ modulation could lead to potent insulin sensitization without adverse effects such as weight gain [32]. Several compounds have now been identified as SPPARMs, and some of them are already in clinical testing [32][33][34][35]. In addition, pan-agonists combining PPARα, γ, and δ agonism have the potential to improve insulin resistance and dyslipidemia without causing weight gain.…”

Section: Ppars Drug Targets For Diabetes and Obesitymentioning

confidence: 99%

Orphan nuclear receptors in drug discovery

Shi

2007

Drug Discovery Today

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SummaryOrphan nuclear receptors provide a unique resource for uncovering novel regulatory systems that impact human health and provide excellent drug targets for a variety of human diseases. Ligands of nuclear receptors have been used in a number of important therapeutic areas, such as breast cancers, skin disorders, and diabetes. Orphan nuclear receptors, therefore, represent a tremendous opportunity in understanding and treating human diseases. This review highlights advances and potentials of using orphan nuclear receptors, in particular PPARs, Nurr1, RORs, and TLX as targets for drug discovery in diabetes and obesity, neurodegenerative diseases, and other related disorders.

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Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor γ agonist, on insulin resistance in Zucker fatty rat

Cited by 34 publications

References 19 publications

The Novel Hypoglycemic Agent YM440 Improves Hepatic Insulin Resistance in Obese Zucker Fatty Rats

The Novel Hypoglycemic Agent YM440 Improves Hepatic Insulin Resistance in Obese Zucker Fatty Rats

Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Phlorotannins from Edible Brown Algae,Ecklonia stoloniferaandEisenia bicyclis

Orphan nuclear receptors in drug discovery

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