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https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#1
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28514806/human-epicardial-fat-expresses-glucagon-like-peptide-1-and-2-receptors-genes
#2
Gianluca Iacobellis, Vladimir Camarena, David W Sant, Gaofeng Wang
Epicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart with unique anatomy, functionality, and transcriptome. EAT can serve as a therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2 receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects with coronary artery disease and type 2 diabetes mellitus undergoing elective cardiac surgery...
May 17, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28514449/human-glp-1-receptor-transmembrane-domain-structure-in-complex-with-allosteric-modulators
#3
Gaojie Song, Dehua Yang, Yuxia Wang, Chris de Graaf, Qingtong Zhou, Shanshan Jiang, Kaiwen Liu, Xiaoqing Cai, Antao Dai, Guangyao Lin, Dongsheng Liu, Fan Wu, Yiran Wu, Suwen Zhao, Li Ye, Gye Won Han, Jesper Lau, Beili Wu, Michael A Hanson, Zhi-Jie Liu, Ming-Wei Wang, Raymond C Stevens
The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are members of the secretin-like class B family of G-protein-coupled receptors (GPCRs) and have opposing physiological roles in insulin release and glucose homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP-1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose-dependent manner. Here we report crystal structures of the human GLP-1R transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28493611/fucoidan-ameliorates-pancreatic-%C3%AE-cell-death-and-impaired-insulin-synthesis-in-streptozotocin-treated-%C3%AE-cells-and-mice-via-a-sirt-1-dependent-manner
#4
Wen-Chun Yu, Yen-Lin Chen, Pai-An Hwang, Tso-Hsiao Chen, Tz-Chong Chou
SCOPE: Several beneficial biological functions of fucoidan (FO) isolated from brown algae have been demonstrated. The purpose of this study was to investigate whether FO derived from Sargassum hemiphyllum ameliorates pancreatic β-cell damage and impaired insulin synthesis under diabetic condition. METHODS AND RESULTS: The effects of FO were studied in streptozotocin (STZ)-treated pancreatic β-cell line, NIT-1cells, and mice. The cell apoptosis, protein analyses, histological examination, and pancreatic function assays were performed...
May 11, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28481334/liraglutide-reduces-body-weight-by-upregulation-of-adenylate-cyclase-3
#5
Z Li, Y Liang, N Xia, Y Lai, H Pan, S Zhou, F Jiang, Y He
OBJECTIVE: According to recent studies, adenylate cyclase 3 (AC3) is associated with obesity. Liraglutide reduces blood glucose levels and body weight (BW). We performed a 2 × 2 factorial experiment to study the relationships among AC3, liraglutide and obesity and to obtain a more comprehensive understanding of the mechanisms underlying the physiological effects of liraglutide on obesity. METHODS: A high-fat diet was used to induce obesity in C57BL/6J mice. Both the normal and obese mice were treated with liraglutide (1 mg kg(-1)) or saline twice daily for 8 weeks...
May 8, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28461695/a-hippocampus-to-prefrontal-cortex-neural-pathway-inhibits-food-motivation-through-glucagon-like-peptide-1-signaling
#6
T M Hsu, E E Noble, C M Liu, A M Cortella, V R Konanur, A N Suarez, D J Reiner, J D Hahn, M R Hayes, S E Kanoski
The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#7
Huashan Gao, Qian Zhao, Ziwei Song, Zhaocong Yang, You Wu, Shanshan Tang, Murad Alahdal, Yanfeng Zhang, Liang Jin
It is well known that glucagon-like peptide 1 (GLP-1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP-1 receptor (GLP-1R) and an insulinomimetic effect independent of GLP-1R. However, use of GLP-1 in vivo is limited by its short half-life. Therefore, our lab designed PGLP-1, a novel 2-function candidate peptide as a potential substitute. Using a streptozotocin-induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP-1 had insulinotropic actions dependent on GLP-1R and insulinomimetic functions independent of GLP-1R...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#8
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28454451/expression-of-glp-1-receptor-and-cd26-in-human-thyroid-c-cells-the-association-of-thyroid-c-cell-tumorigenesis-with-incretin-based-medicine
#9
Yuejia Song, Min Zhou, Yang Cao, Jiping Qi, Jingshu Geng, Xiaomin Liu
Recent reports have demonstrated that long-term and high dosage treatments with incretin-based medicine, such as hormone glucagon-like peptide-1 (GLP-1) may induce thyroid C-cell pathological changes in rodents, rather than in humans. Doubts regarding the tumorigenic potential of GLP-1 analogues in human thyroid C-cells remain. The present study aimed to determine the expression levels of GLP-1 receptor (GLP-1R) and cluster of differentiation 26 (CD26) in the C-cells of thyroid tissues from non-neoplastic, medullary carcinoma and hyperplasia subjects, and to explore the potential clinical significance...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28450048/liraglutide-alleviates-h2o2-induced-retinal-ganglion-cells-injury-by-inhibiting-autophagy-through-mitochondrial-pathways
#10
Xuefei Ma, Wenjian Lin, Zhenyu Lin, Ming Hao, Xinyuan Gao, Yue Zhang, Hongyu Kuang
Retinal ganglion cells (RGCs), which exist in the inner retina, are the retinal neurons which can be damaged in the early stage of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, exerts biological functions by binding the receptor (GLP-1R), the expression of which in RGC-5 cells was first shown by our team in 2012. It was reported that liraglutide prevented retinal neurodegeneration in diabetic subjects. However, the involvement of mechanisms such as autophagy and mitochondrial balance in liraglutide-induced retinal protection is unknown...
April 24, 2017: Peptides
https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#11
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28443255/glucagon-like-peptide-1-and-glucagon-like-peptide-1-receptor-agonists-in-the-treatment-of-type-2-diabetes
#12
REVIEW
Seungah Lee, Dong Yun Lee
The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic β-cell insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide...
March 2017: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#13
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#14
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#15
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28400403/molecular-imaging-in-the-investigation-of-hypoglycaemic-syndromes-and-their-management
#16
David A Pattison, Rodney J Hicks
There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors - somatostatin receptors (SSTR) and glucagon-like peptide-1 receptor (GLP-1R) - the Amine Precursor Uptake and Decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]Fluoro-2-Deoxy-D-Glucose (FDG)...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28375405/hot-topics-in-primary-care-titratable-fixed-ratio-combinations-in-type-2-diabetes-mellitus-focus-on-glp-1r-agonists-combined-with-basal-insulin
#17
REVIEW
James LaSalle, John R White
The treatment of hyperglycemia in patients without glycemic control despite metformin monotherapy is the focus of this article, with particular focus on the use of fixed-dose (FDC) and fixed-ratio combination products.
April 2017: Journal of Family Practice
https://www.readbyqxmd.com/read/28368447/co-expressed-class-b-g-protein-coupled-secretin-and-glp-1-receptors-self-and-cross-associate-impact-on-pancreatic-islets
#18
Kaleeckal G Harikumar, Shannen Lau, Patrick M Sexton, Denise Wootten, Laurence J Miller
Class B GPCRs form symmetrical homo-dimeric complexes along the lipid face of transmembrane segment 4, and can form hetero-dimeric complexes, although their structure is unknown. The current study demonstrates that the lipid face of TM4 is also the predominant determinant for formation of hetero-receptor complexes between two class B receptors, secretin receptor (SecR) and glucagon-like peptide-1 receptor (GLP-1R), expressed on pancreatic islet cells. Since these receptors use the same interface for formation of homo- and hetero-receptor complexes, there might be competitive forces affecting expression of different complexes...
March 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28363772/characterization-of-signal-bias-at-the-glp-1-receptor-induced-by-backbone-modification-of-glp-1
#19
Marlies V Hager, Lachlan Clydesdale, Samuel H Gellman, Patrick M Sexton, Denise Wootten
The glucagon-like peptide-1 receptor (GLP-1R) is a cla B G protein-coupled receptor that is a major therapeutic target for the treatment of type 2 diabetes. Activation of this receptor promotes insulin secretion and blood glucose regulation. The GLP-1R can initiate signaling through several intracellular pathways upon activation by GLP-1. GLP-1R ligands that preferentially stimulate subsets among the natural signaling pathways ("biased agonists") could be useful as tools for elucidating the consequences of specific pathways and might engender therapeutic agents with tailored effects...
March 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28337255/combined-therapy-with-melatonin-and-exendin-4-effectively-attenuated-the-deterioration-of-renal-function-in-rat-cardiorenal-syndrome
#20
Kuan-Hung Chen, Chih-Hung Chen, Christopher Glenn Wallace, Yen-Ta Chen, Chih-Chao Yang, Pei-Hsun Sung, Hsin-Ju Chiang, Yi-Ling Chen, Sarah Chua, Hon-Kan Yip, Jiin-Tsuey Cheng
This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4...
2017: American Journal of Translational Research
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