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Glucagon like peptide

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https://www.readbyqxmd.com/read/28533434/lysophosphatidylinositol-induced-activation-of-the-cation-channel-trpv2-triggers-glucagon-like-peptide-1-secretion-in-enteroendocrine-l-cells
#1
Kazuki Harada, Tetsuya Kitaguchi, Taichi Kamiya, Kyaw Htet Aung, Kazuaki Nakamura, Kunihiro Ohta, Takashi Tsuboi
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+]i) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#2
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/28530382/diabetes-update-new-pharmacotherapy-for-type-2-diabetes
#3
Beth Choby
Multiple new drugs for managing type 2 diabetes have entered the market in the past 5 years. Guidelines from the American Diabetes Association recommend metformin for initial therapy, followed by a second drug if A1c goals are not met or initially for patients with A1c levels greater than 9%. Conversely, the American Association of Clinical Endocrinologists recommends initial management with two drugs if the A1c level is greater than 7.5%. The risk of lactic acidosis associated with metformin has been shown to be less than previously thought, with newer guidelines permitting use with an estimated glomerular filtration rate of 45 to 60 mL/min/1...
May 2017: FP Essentials
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#4
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526920/effects-of-semaglutide-on-beta-cell-function-and-glycaemic-control-in-participants-with-type-2-diabetes-a-randomised-double-blind-placebo-controlled-trial
#5
Christoph Kapitza, Kirsten Dahl, Jacob B Jacobsen, Mads B Axelsen, Anne Flint
AIMS/HYPOTHESIS: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed. METHODS: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA1c of 6...
May 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#6
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28526379/the-polish-intestinal-failure-centres-consensus-on-the-use-of-teduglutide-for-the-treatment-of-short-bowel-syndrome
#7
Stanisław Klek, Marek Kunecki, Jacek Sobocki, Konrad Matysiak, Katarzyna Karwowska, Krystyna Urbanowicz
OBJECTIVE: Teduglutide is an active, glucagon-like peptide (GLP)-2 analog with proven clinical efficacy regarding intestinal adaptation in patients with short bowel syndrome (SBS). There are two factors that preclude its reimbursement, and thereby, its availability: its cost (reaching ∼$300,000/y)-which significantly exceeds the cost of home parenteral nutrition (HPN) in most countries-and the lack of clear guidelines. The aim of this study was to create evidence-based working criteria for the use of teduglutide that could be used in clinical settings...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28526033/effects-of-exenatide-on-cardiac-function-perfusion-and-energetics-in-type-2-diabetic-patients-with-cardiomyopathy-a-randomized-controlled-trial-against-insulin-glargine
#8
Weena J Y Chen, Michaela Diamant, Karin de Boer, Hendrik J Harms, Lourens F H J Robbers, Albert C van Rossum, Mark H H Kramer, Adriaan A Lammertsma, Paul Knaapen
BACKGROUND: Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored...
May 19, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28523587/erratum-to-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-the-brain-adipocyte-axis
#9
Bruno Geloneze, José Carlos de Lima-Júnior, Lício A Velloso
No abstract text is available yet for this article.
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#10
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523483/modeling-the-long-term-cost-effectiveness-of-ideglira-in-patients-with-type-2-diabetes-who-are-failing-to-meet-glycemic-targets-on-basal-insulin-alone-in-the-netherlands
#11
Barnaby Hunt, Divina Glah, Maarten van der Vliet
INTRODUCTION: Insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single pen injection device, and a once-daily treatment option for patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on basal insulin and require treatment intensification. The objective of this analysis was to evaluate the long-term cost-effectiveness of IDegLira versus basal-bolus therapy (insulin glargine U100 + 3× daily insulin aspart) for patients with T2DM uncontrolled on basal insulin [HbA1c >53 mmol/mol (>7%)] in the Netherlands...
May 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28522195/a-dpp-iv-resistant-glucagon-like-peptide-2-dimer-with-enhanced-activity-against-radiation-induced-intestinal-injury
#12
Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly(2)]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28515711/the-impact-of-glucagon-like-peptide-1-on-bone-metabolism-and-its-possible-mechanisms
#13
REVIEW
Chenhe Zhao, Jing Liang, Yinqiu Yang, Mingxiang Yu, Xinhua Qu
The impact of antidiabetic drugs on bone metabolism is drawing increasing attention due to the discovery of a correlation between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel and promising class of drugs for T2DM, which may also have clinical applications in bone tissue disorders. This review examines the impact of GLP-1 on bone metabolism, including enhancement of bone mineral density and improvement of bone quality. However, the precise effect of GLP-1 on fracture risk has not been unambiguously defined...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28514806/human-epicardial-fat-expresses-glucagon-like-peptide-1-and-2-receptors-genes
#14
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
#15
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/28513427/population-pharmacokinetics-of-lyophilized-recombinant-glucagon-like-peptide-1-receptor-agonist-recombinant-exendin-4-re-4-in-chinese-patients-with-type-2-diabetes-mellitus%C3%A2
#16
Yan-Nan Zang, Min-Jie Zhang, Yi-Tong Wang, Chen Wang, Qian Wang, Qing-Shan Zheng, Li-Nong Ji, Wei Guo, Yi Fang
OBJECTIVE: To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment. METHODS: Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%...
May 17, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#17
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28510260/markers-of-enteral-adaptation-in-pediatric-cases-with-short-bowel-syndrome
#18
Masahiro Chiba, Yutaka Sanada, Akira Toki
BACKGROUND: This study aimed to ascertain if prospective determinations of specific gut hormones and growth factors could predict bowel adaptation in children with short bowel syndrome (SBS). METHODS: We studied parenteral nutrition (PN) independency as the short-term result and discontinuation of enteral nutrition (EN) as the long-term result from a retrospective chart review of 7 patients with SBS, who were managed in the absence of growth retardation. The correlation between increased numbers of enteral feedings or enteral nutrients and fasting levels of serum gastrin, glucagon-like peptide 2 (GLP-2), citrulline, and diamine oxidase (DAO) activity was analyzed...
May 16, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28507060/alogliptin-a-dipeptidyl-peptidase-4-inhibitor-alleviates-atrial-remodeling-and-improves-mitochondrial-function-and-biogenesis-in-diabetic-rabbits
#19
Xiaowei Zhang, Zhiwei Zhang, Yungang Zhao, Ning Jiang, Jiuchun Qiu, Yajuan Yang, Jian Li, Xue Liang, Xinghua Wang, Gary Tse, Guangping Li, Tong Liu
BACKGROUND: There is increasing evidence implicating atrial mitochondrial dysfunction in the pathogenesis of atrial fibrillation. In this study, we explored whether alogliptin, a dipeptidyl peptidase-4 inhibitor, can prevent mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model. METHODS AND RESULTS: A total of 90 rabbits were randomized into 3 groups as follows: control group (n=30), alloxan-induced diabetes mellitus group (n=30), and alogliptin-treated (12...
May 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28506816/ghrelin-suppresses-cholecystokinin-cck-peptide-yy-pyy-and-glucagon-like-peptide-1-glp-1-in-the-intestine-and-attenuates-the-anorectic-effects-of-cck-pyy-and-glp-1-in-goldfish-carassius-auratus
#20
Ayelén Melisa Blanco, Juan Ignacio Bertucci, Ana Isabel Valenciano, María Jesús Delgado, Suraj Unniappan
Ghrelin is an important gut-derived hormone with an appetite stimulatory role, while most of the intestinal hormones, including cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether these important peptides with opposing roles on food intake interact to regulate energy balance in fish is currently unknown. The aim of this study was to characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in goldfish (Carassius auratus). We first determined the localization of CCK, PYY and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone secretagogue 1a) in the goldfish intestine by immunohistochemistry...
May 18, 2017: Hormones and Behavior
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