Synthesis and in vitro biological evaluation of new pyrimidines as glucagon-like peptide-1 receptor agonists

2017 ◽  
Vol 27 (22) ◽  
pp. 5071-5075 ◽  
Author(s):  
Shaikha S. AlNeyadi ◽  
Abdu Adem ◽  
Naheed Amer ◽  
Alaa A. Salem ◽  
Ibrahim M. Abdou
Keyword(s):  
Biological Evaluation ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

2019 ◽  
Vol 105 (4) ◽  
pp. e1549-e1560 ◽  
Author(s):  
Bénédicte Gaborit ◽  
Jean-Baptiste Julla ◽  
Samaher Besbes ◽  
Matthieu Proust ◽  
Clara Vincentelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Fundus Photography ◽  
Endothelial Cell Proliferation ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Aims Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. Methods We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. Results In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800–1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. Conclusions The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

scholarly journals Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists

2013 ◽  
Vol 37 (5) ◽  
pp. 588-599 ◽  
Author(s):  
Yu-Juan Zhang ◽  
Liu-Lan Shen ◽  
Hyae-Gyeong Cheon ◽  
Yong-Nan Xu ◽  
Jin-Hyun Jeong
Keyword(s):  
Biological Evaluation ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Synthesis And Biological Evaluation

scholarly journals The Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 Inhibits Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption via Inhibition of TNF-αExpression in Macrophages

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wei-Ren Shen ◽  
Keisuke Kimura ◽  
Masahiko Ishida ◽  
Haruki Sugisawa ◽  
Akiko Kishikawa ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Mrna Expression ◽  
Receptor Agonist ◽  
Type I Collagen ◽  
Osteoclast Formation ◽  
Type I ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) receptor agonists are an effective treatment approach for type 2 diabetes. Recently, anti-inflammatory effects of GLP-1 receptor agonists have also been reported. Lipopolysaccharide (LPS) induces inflammation and osteoclast formation. In this study, we investigated the effect of exendin-4, a widely used GLP-1 receptor agonist, in LPS-induced osteoclast formation and bone resorption. LPS with or without exendin-4 was administered on mouse calvariae by daily subcutaneous injection. The number of osteoclasts, the ratio of bone resorption pits, and the level of C-terminal cross-linked telopeptide of type I collagen (CTX) were significantly lower in LPS- and exendin-4-coadministered mice than in mice administered with LPS alone. RANKL and TNF-αmRNA expression levels were lower in the exendin-4- and LPS-coadministered group than in the LPS-administered group. Ourin vitroresults showed no direct effects of exendin-4 on RANKL-induced osteoclast formation, TNF-α-induced osteoclast formation, or LPS-induced RANKL expression in stromal cells. Conversely, TNF-αmRNA expression was inhibited in the exendin-4- and LPS-cotreated macrophages compared with cells treated with LPS alone. These results indicate that the GLP-1 receptor agonist exendin-4 may inhibit LPS-induced osteoclast formation and bone resorption by inhibiting LPS-induced TNF-αproduction in macrophages.

scholarly journals The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

2020 ◽  
Vol 21 (8) ◽  
pp. 2854 ◽  
Author(s):  
Shiqi Luo ◽  
Harsharn Gill ◽  
Bryce Feltis ◽  
Andrew Hung ◽  
Linh Toan Nguyen ◽  
...  
Keyword(s):  
Weight Loss ◽  
Active Form ◽  
Receptor Activation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Published Data ◽  
Herbal Formula ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The herbal formula RCM-107 has demonstrated its inhibitory effects on lipid and carbohydrate absorption in our previous work. However, no published data described its effects on GLP-1 secretion. Therefore, this study aimed to determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion via enzyme-linked immunosorbent assay (ELISA). Furthermore, molecular docking was performed to predict the key chemical compounds that are likely to be GLP-1 receptor agonists. Gardeniae fructus, one of the ingredients in RCM-107, demonstrated significantly greater effects on inducing GLP-1 secretion than the positive control epigallocatechin gallate (EGCG). Two Gardeniae fructus ligands, 3-epioleanolic acid and crocin were predicted to bind to the active form of GLP-1 receptor at the binding pocket with residues known for the receptor activation, suggesting that they could potentially serve as receptor agonists. Overall, this study reported the effects of researched herbs on GLP-1 secretion and proposed two compounds that may be responsible for antiobesity via GLP-1 receptor activation.

Patient-Reported Outcomes following Initiation of Glucagon-Like Peptide-1 Receptor AgonistS (GLP–1RA) in PatientS with Type 2 Diabetes—PROGRESS-DIABETES Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1096-P
Author(s):  
RUTH E. BROWN ◽  
ALEXANDER ABITBOL ◽  
HARPREET S. BAJAJ ◽  
HASNAIN KHANDWALA ◽  
RONALD GOLDENBERG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Reported Outcomes ◽  
Receptor Agonists ◽  
Patient Reported ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Fat Mass ◽  
Body Fat Mass ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

974-P: Network Meta-analysis of Once Weekly Glucagon-Like Peptide-1 Receptor Agonists: A Focus on Cardiovascular Safety and Mortality

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 974-P
Author(s):  
OSAMAH ALFAYEZ ◽  
OMAR A. ALMOHAMMED ◽  
OMAR ALKHEZI ◽  
MAJED S. AL YAMI
Keyword(s):  
Meta Analysis ◽  
Cardiovascular Safety ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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