Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR蓱/) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse effects. Here we report the design and preclinical...
李瑞芳等证明了非诺贝特激活PPAR-α后可以通过调控转录因子NFATc4来抑制ET-1诱导的心肌肥大反应[3]。胰高血糖素样肽-1 (GLP-1) 是一种是由肠道内L细胞分泌的一种十分重要的肠促胰岛素, 其受体激动剂Exendin-4是由动物唾液分泌的GLP-1类似物[4,5]。近年来对GLP-1的研究发现其对心血管系统具有保护作用, 如...
Devasthale et al., “Discovery of tertiary aminoacids as dual PPARα/γ agonists-I,” Bioorganic & Medicinal Chemistry Letters 17:2312-2316, 2007. International Search Report and Written Opinion, dated Dec. 1, 2011, for International Application No. PCT/US2011/039873, 9 pages. Knudsen et...
P124The ppargamma agonist pioglitazone reverses pulmonary arterial hypertension (PAH) and prevents right heart failure through fatty acid oxidation (fao) Purpose: So far, no intervention could fully reverse PAH or even prevent pressure overload heart failure, in the well-established SuHx rat model ...
In a 3xTg-AD mouse model, exenatide treatment reversed high fat diet-induced impairments of BDNF signaling and reduced levels of NF-κB and peroxisome proliferator-activated receptor proteins (PPARs) α and γ, indicating reduced inflammation; however, there was no significant effect on systemic ...
Insulin sensitizers. Insulin sensitizers are drugs that enhance the body's response to insulin. Thiozolidinediones such as Avandia™ (rosiglitazone) and Actos™ activate peroxisome proliferator-activated receptor (PPAR) gamma and modulate the activity of a set of genes that have not been well de...
The KEGG analyses revealed that insulin-signaling-related PI3K-AKT pathway, PPAR signaling, and several lipid-metabolism-related pathways, including GL metabolism and cholesterol metabolism (Figure 7B), are among the top enriched pathways in the SAT. We then analyzed the genes that were significantly...
Brand CL, Galsgaard ED, Tornehave D, Romer J, Gotfredsen CF, Wassermann K, Knudsen LB, Volund A and Sturis J: Synergistic effect of the human GLP‑1 analogue liraglutide and a dual PPARalpha/gamma agonist on glycaemic control in Zucker diabetic fatty rats. Diabetes...
Given that the likely dominant mode of action of gut hormone agonists is upstream on weight, initial combinations might focus on agents which have been shown to have a more direct effect on fibrosis, which would include FGF21 (fibroblast growth factor 21) agonists and the pan-PPAR (peroxisome...
[22,23]. Interestingly, in a PD rat model, the activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ), which increases insulin sensitization and glucose metabolism, protected against MPTP-induced memory impairment [24]. Additionally, in a recent 6-OHDA PD rat model study, ...