The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells

2014 ◽  
Vol 451 (2) ◽  
pp. 339-344 ◽  
Author(s):  
Hirohisa Onuma ◽  
Kouichi Inukai ◽  
Atsuko Kitahara ◽  
Rie Moriya ◽  
Susumu Nishida ◽  
...  
2005 ◽  
Vol 289 (3) ◽  
pp. R729-R737 ◽  
Author(s):  
Karine Proulx ◽  
Daniela Cota ◽  
Tamara R. Castañeda ◽  
Matthias H. Tschöp ◽  
David A. D'Alessio ◽  
...  

Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-α. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-α agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.


2018 ◽  
Vol 50 (2) ◽  
pp. 679-693 ◽  
Author(s):  
Yue Yao ◽  
Qiang Li ◽  
Wei Wang ◽  
Jinchao Zhang ◽  
Ping Gao ◽  
...  

Background/Aims: Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. Methods: Cell viability was determined by CCK-8. Caspase-3 detection was used to assess the effects of GLP-1 on cholesterol-induced apoptosis. TNF-α and IL-6 as the inflammatory markers were measured by ELISA. The alterations of miR-19b and ATP-binding cassette transporter A1 (ABCA1) resulting from high-fat diet/cholesterol incubation or GLP-1 were detected by real-time PCR and western blot. Results: GLP-1 markedly up-regulated the expression of ABCA1 protein, but didn’t affect peroxisome proliferator-activated receptor α (PPAR-α) protein. The miR-19b levels were significantly down-regulated in GLP-1-treated groups. The inhibition and overexpression of miR-19b were established to explore the effects of a GLP-1-mediated alteration in miR-19b. Cholesterol transport assays revealed that treatment with GLP-1 alone or together with miR-19b inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Further, histological examination was used to detect lipid accumulation. Cholesterol significantly attenuated cell viability, promoted hepatic cell apoptosis, and facilitated lipid accumulation, and these effects could be reversed by GLP-1. Conclusion: GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-19b and ABCA1.


2020 ◽  
Vol 26 (39) ◽  
pp. 4992-5001
Author(s):  
Xin Wang ◽  
Jinhong Kang ◽  
Qing Liu ◽  
Tao Tong ◽  
Helong Quan

Background: The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges. Objectives: This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus. Methods: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc. Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5′-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed. Conclusion: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.


2020 ◽  
Vol 9 (2) ◽  
pp. 49-58
Author(s):  
A.S. Ametov ◽  
◽  
A.O. Nevolnikova ◽  
E.A. Tertychnaya ◽  
O.A. Mishra ◽  
...  

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