scholarly journals The class B G-protein-coupled GLP-1 receptor: an important target for the treatment of type-2 diabetes mellitus

2014 ◽  
Vol 4 (S1) ◽  
pp. S9-S13 ◽  
Author(s):  
L J Miller ◽  
P M Sexton ◽  
M Dong ◽  
K G Harikumar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
Important Target ◽  
Class B ◽  
G Protein Coupled

scholarly journals G protein-coupled receptor 119 agonist DS-8500a effects on pancreatic β-cells in Japanese type 2 diabetes mellitus patients

2018 ◽  
Vol 10 (1) ◽  
pp. 84-93 ◽  
Author(s):  
Hirotaka Watada ◽  
Masanari Shiramoto ◽  
Shin Irie ◽  
Yasuo Terauchi ◽  
Yuichiro Yamada ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
G Protein Coupled

GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus

2013 ◽  
Vol 15 (11) ◽  
pp. 1013-1021 ◽  
Author(s):  
R. L. Dobbins ◽  
S. P. Shearn ◽  
R. L. Byerly ◽  
F. F. Gao ◽  
K. M. Mahar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
Serum Glucose ◽  
G Protein Coupled Receptor ◽  
Selective Agonist ◽  
G Protein Coupled

scholarly journals De novo Design of G Protein-Coupled Receptor 40 Peptide Agonists for Type 2 Diabetes Mellitus Based on Artificial Intelligence and Site-Directed Mutagenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xu Chen ◽  
Zhidong Chen ◽  
Daiyun Xu ◽  
Yonghui Lyu ◽  
Yongxiao Li ◽  
...  
Keyword(s):  
Neural Network ◽  
Diabetes Mellitus ◽  
Machine Learning ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
G Protein Coupled

G protein-coupled receptor 40 (GPR40), one of the G protein-coupled receptors that are available to sense glucose metabolism, is an attractive target for the treatment of type 2 diabetes mellitus (T2DM). Despite many efforts having been made to discover small-molecule agonists, there is limited research focus on developing peptides acting as GPR40 agonists to treat T2DM. Here, we propose a novel strategy for peptide design to generate and determine potential peptide agonists against GPR40 efficiently. A molecular fingerprint similarity (MFS) model combined with a deep neural network (DNN) and convolutional neural network was applied to predict the activity of peptides constructed by unnatural amino acids (UAAs). Site-directed mutagenesis (SDM) further optimized the peptides to form specific favorable interactions, and subsequent flexible docking showed the details of the binding mechanism between peptides and GPR40. Molecular dynamics (MD) simulations further verified the stability of the peptide–protein complex. The R-square of the machine learning model on the training set and the test set reached 0.87 and 0.75, respectively; and the three candidate peptides showed excellent performance. The strategy based on machine learning and SDM successfully searched for an optimal design with desirable activity comparable with the model agonist in phase III clinical trials.

scholarly journals G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

2017 ◽  
Vol 70 (1) ◽  
pp. 39-67 ◽  
Author(s):  
Darren M. Riddy ◽  
Philippe Delerive ◽  
Roger J. Summers ◽  
Patrick M. Sexton ◽  
Christopher J. Langmead
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

scholarly journals YH18968, a Novel 1,2,4-Triazolone G-Protein Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes Mellitus

2018 ◽  
Vol 26 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Taedong Han ◽  
Byoung Moon Lee ◽  
Yoo Hoi Park ◽  
Dong Hoon Lee ◽  
Hyun Ho Choi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Glucagon and Glucagon-like Peptide-1 Receptors: Promising Therapeutic Targets for an Effective Management of Diabetes Mellitus

2020 ◽  
Vol 26 (4) ◽  
pp. 501-508
Author(s):  
Ghulam Abbas ◽  
Quazi M. I. Haq ◽  
Ahmad Hamaed ◽  
Mohammed Al-Sibani ◽  
Hidayat Hussain
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
G Protein ◽  
Treatment Modalities ◽  
Normal Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

: G-protein-coupled receptors (GPCRs) are membrane-bound proteins, which are responsible for the detection of extracellular stimuli and the origination of intracellular responses. Both glucagon and glucagon-like peptide-1 (GLP-1) receptors belong to G protein-coupled receptor (GPCR) superfamily. Along with insulin, glucagon and GLP-1 are critical hormones for maintaining normal serum glucose within the human body. Glucagon generally plays its role in the liver through cyclic adenosine monophosphate (cAMP), where it compensates for the action of insulin. GLP-1 is secreted by the L-cells of the small intestine to stimulate insulin secretion and inhibit glucagon action. Despite extensive research efforts and the multiple approaches adopted, the glycemic control in the case of type-2 diabetes mellitus remains a major challenge. Therefore, a deep understanding of the structure-function relationship of these receptors will have great implications for future therapies in order to maintain a normal glucose level for an extended period of time. The antagonists of glucagon receptors that can effectively block the hepatic glucose production, as a result of glucagon action, are highly desirable for the tuning of the hyperglycemic state in type 2 diabetes mellitus. In the same manner, GLP-1R agonists act as important treatment modalities, thanks to their multiple anti-diabetic actions to attain normal glucose levels. : In this review article, the structural diversity of glucagon and GLP-1 receptors along with their signaling pathways, site-directed mutations and significance in drug discovery against type-2 diabetes are illustrated. Moreover, the promising non-peptide antagonists of glucagon receptor and agonists of GLP-1 receptor, for the management of diabetes are presented with elaboration on the structure-activity relationship (SAR).

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