TY - JOUR. T1 - Effect of Glepaglutide, a Long-Acting Glucagon-Like Peptide-2 Analog, on Gastrointestinal Transit Time and Motility in Patients With Short Bowel Syndrome. T2 - Findings From a Randomized Trial. AU - Hvistendahl, Mark Krogh. AU - Naimi, Rahim Mohammad. AU - Enevoldsen, Lotte Hahn. AU - Madsen, Jan Lysgaard. AU - Fuglsang, Stefan. AU - Jeppesen, Palle Bekker. N1 - © 2020 American Society for Parenteral and Enteral Nutrition.. PY - 2020/11. Y1 - 2020/11. N2 - BACKGROUND: Patients with short bowel syndrome (SBS) and distal-bowel resections lack neuroendocrine feedback regulations, potentially resulting in rapid gastrointestinal (GI) transit. The objective was to assess the efficacy of glepaglutide, a long-acting glucagon-like peptide-2 analog, on GI transit in patients with SBS.METHODS: In this single-center, double-blind, dose-finding, phase 2 trial, patients with SBS were randomly assigned to 3 treatments (0.1, 1, and 10 mg) in a 2-period crossover design. Each treatment period ...
TY - JOUR. T1 - Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation. AU - Koole, Cassandra. AU - Wootten, Denise. AU - Simms, John. AU - Valant, Celine. AU - Miller, Laurence J. AU - Christopoulos, Arthur. AU - Sexton, Patrick. PY - 2011. Y1 - 2011. N2 - The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full length (1-37) and truncated (7-37) forms of GLP-1 that can exist in an amidated form (GLP-1(1-36)NH(2) and GLP-1(7-36)NH(2)), and the related peptide oxyntomodulin. In addition, the GLP-1R possesses exogenous agonists, including exendin-4, and the allosteric modulator, compound 2 (6,7-dichloro2-methylsulfonyl-3-tert-butylaminoquinoxaline). The complexity of ...
Peptides , Glucagon-Like Peptides , Glucagon-Like Peptide 1, GLP-1 amide, human, FAM-labeled; This is fluorescent GLP-1 labeled at the peptide C-terminus with FAM, Abs/Em=494/521 nm. In response to Glucose ingestion, proglucagon in the intestinal L cells is cleaved into GLP-1 (1-36). Prior to secretion into the circulation, GLP-1 (1-36) is further processed into amidated GLP-1 (7-36)-cat# AS-22462-and small amounts of glycine-extended GLP-1 (7-37)-cat# AS-20761. Both GLP-1 (7-36) and GLP-1 (7-37), causes glucose dependent release of insulin by pancreatic beta-cells. They also play a role in gastric motility (gastric emptying), on the suppression of plasma glucagon levels (glucose production) and possibly on the promotion of satiety and stimulation of glucose disposal in peripheral tissues independent of the actions of insulin. GLP-1 peptides such as GLP-1 (1-36) have been used to investigate restoration of pancreatic beta cell function. GLP-1 is also produced in the central nervous system. ; FAM
Background: The incretin hormone glucagon-like peptide-1 (GLP-1) appears to enhance myocardial glucose uptake, which may reduce fatty acid oxidation and improve myocardial tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, also stimulates this metabolic change, but may also have deleterious effects on left ventricular (LV) function. We hypothesized that GLP-1 would improve myocardial function in the setting of hyperglycemia during dobutamine stress echocardiography (DSE) in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).. METHODS: 10 patients (age 66 ± 5 years, all male) with T2DM, obstructive CAD and normal resting LV systolic function underwent two DSE (in randomized order) during the steady-state phase of a hyperglycemic clamp. During one of the scans, intravenous GLP-1 was infused concomitantly at 1.2pmol/kg/min, and the other scan acted as a control. Tissue Doppler imaging was acquired in 3 apical views at rest, peak stress and 30 ...
In the present study, we investigated the effects of 1 week of treatment with the GLP-1 derivative liraglutide (NN2211) on 24-h substrate and hormone profiles under conditions that simulate daily living, on EGR, and on pancreatic islet cell function. A major finding is a markedly reduced circadian plasma glucose level during liraglutide treatment exhibited by fasting, prandial, and nocturnal concentrations. When evaluating the average reduction in plasma glucose (∼2 mmol/l), it is important to emphasize that 6 of the 13 patients, even after OHA withdrawal, had a fasting plasma glucose ,8.3 mmol/l, i.e., the level above which action should be taken (26). Moreover, this 1-week study was probably too brief to harvest the additional advantageous effects of decreased glucose toxicity, i.e., no improvement in insulin sensitivity. Finally, the same dose (6 μg/kg body wt) of liraglutide was used in all patients. It is likely that some patients would have a further improvement in blood glucose ...
Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a disorder of glucose homeostasis characterized by hyperglycaemia, peripheral insulin resistance, impaired hepatic glucose metabolism, and diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Glucagon-like-p …
L-glutamine stimulates glucagon-like peptide 1 (GLP-1) secretion in individual content and cell lines. for Na+ reliant uptake and Ca2+ influx. The higher efficiency of glutamine being a secretagogue was paralleled by its capability to boost cAMP in GLUTag cells. Glutamine raised intracellular cAMP to 36% of this made by a maximal stimulus, whereas asparagine just elevated intracellular cAMP by 24% and phenylalanine was without impact. Glutamine elevates both cytosolic cAMP and Ca2+ in L cells, which may take into account the potency of glutamine being a GLP-1 secretagogue. Healing realtors like glutamine that focus on synergistic pathways in L cells might play another role in the treating type 2 diabetes. Glucagon-like peptide 1 (GLP-1) is normally synthesized in and secreted from enteroendocrine L cells, which can be found through the entire intestine but mostly found even more distally in the ileum and digestive tract (1). GLP-1 is normally released after nutritional ingestion and mediates ...
TY - JOUR. T1 - SAD-A Potentiates Glucose-Stimulated Insulin Secretion as a Mediator of Glucagon-Like Peptide 1 Response in Pancreatic β Cells. AU - Nie, Jia. AU - Lilley, Brendan N.. AU - Pan, Y. Albert. AU - Faruque, Omar. AU - Liu, Xiaolei. AU - Zhang, Weiping. AU - Sanes, Joshua R.. AU - Han, Xiao. PY - 2013/7/1. Y1 - 2013/7/1. N2 - Type 2 diabetes is characterized by defective glucose-stimulated insulin secretion (GSIS) from pancreatic cells, which can be restored by glucagon-like peptide 1 (GLP-1), an incretin hormone commonly used for the treatment of type 2 diabetes. However, molecular mechanisms by which GLP-1 affects glucose responsiveness in islet β cells remain poorly understood. Here we investigated a role of SAD-A, an AMP-activated protein kinase (AMPK)-related kinase, in regulating GSIS in mice with conditional SAD-A deletion. We show that selective deletion of SAD-A in pancreas impaired incretins effect on GSIS, leading to glucose intolerance. Conversely, overexpression of ...
GLP-1(28-36)amide, the Glucagon-like peptide-1 metabolite: friend, foe, or pharmacological folly? Meng-Wong Taing,1,2 Felicity J Rose,1,3 Jonathan P Whitehead11Metabolic Medicine, Mater Research Institute, University of Queensland, 2School of Pharmacy, University of Queensland, Brisbane, QLD, Australia; 3University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, AustraliaAbstract: The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes. GLP-1 mediates its key insulinotropic effects via a G-protein coupled receptor expressed on β-cells and other pancreatic cell types. The insulinotropic activity of GLP-1 is terminated via enzymatic cleavage by dipeptidyl peptidase-4. Until recently, GLP-1-derived metabolites were generally considered metabolically inactive; however, accumulating evidence indicates some have biological activity that may contribute to the pleiotropic effects of GLP-1 independent of the
Glucagon-like peptide (GLP)-1 analogs have been implicated as a risk factor for pancreatitis in humans. We investigated whether liraglutide, the once-daily human GLP-1 analog, induces pancreatitis in rats, mice, and monkeys. Pancreata from mice, rats
The GLP-1 ELISA uses two highly specific antibodies to the active forms of human Glucagon-Like Peptide-1 or GLP-1 in EDTA-plasma.
Glucagon-like peptide 2 (GLP-2) is a recently identified intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. Currently Glucagon-Like Peptide 2 is used as a potential therapeutic agent for the human s...
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Context. Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility.. Objective. Investigate whether physiological plasma concentrations of GLP-1 can inhibit human postprandial gastrointestinal motility; determine target mechanism of GLP-1 and analogue ROSE-010 action.. Design. Single-blind parallel study.. Setting. University research laboratory.. Participants. Healthy volunteers investigated with antroduodenojejunal manometry. Human gastric, intestinal and colonic muscle strips.. Interventions. Motility indices (MI) obtained before and during infusion of saline or GLP-1 were compared. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips, pre-contracted with bethanechol/electric field stimulation (EFS), investigated for GLP-1- or ROSE-010-induced relaxation. GLP-1, GLP-2 and their receptors localized by immunohistochemistry. Action mechanisms studied employing exendin(9-39)amide, ...
The glucagon-like peptide 1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of G protein-coupled receptors. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism. GLP1R binds glucagon-like peptide-1 (GLP1) and glucagon as its natural endogenous agonists. Receptor agonists: GLP-1 - endogenous in humans glucagon - endogenous in humans liraglutide exendin-4, lixisenatide Receptor antagonists: T-0632 Receptor positive allosteric ...
article: The effects of Glucagon Like Peptide-1 (GLP-1) on cardiac remodelling: exploring the role of medication and physiological modulation after metabolic surgery: a narrative review - Minerva Endocrinology 2021 Mar 16 - Minerva Medica - Riviste
In response to ingestion of nutrients, enteroendocrine L cells secrete the incretin hormone, glucagon-like peptide-1 (GLP-1), to enhance glucose-dependent insulin release. Therapies related to GLP-1 are approved for type 2 diabetes. The GLP-1 receptor (GLP-1R) is expressed in cells of the gastrointestinal tract and elsewhere. In pancreatic beta cells, GLP-1R are coupled to the Gs/cAMP/PKA pathway. The expression and function of GLP-1R in gastrointestinal smooth muscle are not known. Aim. To test the hypothesis that GLP-1 regulates smooth muscle function by acting on GLP-1R expressed on smooth muscle. Methods. Smooth muscle cells (SMC) were isolated and cultured. Expression of GLP-1R mRNA was measured by RT-PCR. Expression of GLP-1R protein was measured by western blot. The effect of GLP-1 (7-36) amide on Gαs activation, cAMP formation, and PKA activity was examined in cultured SMC. The effect of GLP-1 on basal activity and on acetylcholine-induced contraction was measured in intact colon via organ bath
Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbAlc 11.6±1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol ×kg−1×min−1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1±0.6 mmol/l). In all patients, insulin (by 17.4±4.7 nmol ×1−1×min; p=0.0157) and C-peptide (by 228.0±39.1 nmol×1−1×min; p=0.0019) increased significantly over ...
Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the KATP channel blocker tolbutamide, and the L-type Ca(2+) channel blocker isradipine; however, depolarization was abolished by
BACKGROUND & AIMS: Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH. METHODS: Fourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes. RESULTS: Liraglutide reduced BMI (-1.9 vs. +0.04kg/m(2); p|0.001), HbA1c (-0.3 vs. +0.3%; p|0.01), cholesterol-LDL (-0.7 vs. +0.05mmol/L;
OBJECTIVE: Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects. RESULTS: Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, ...
Description Liraglutide (LRT) ELISA Kit is an ELISA kit for the quantitative in vitro measurement of liraglutide (LRT) concentrations in serum, plasma, tissue homogenates, cell lysates, cell culture supernatants, and other biological fluids. Introduction Liraglutide (NN2211) is a derivative of human incretin (metabolic hormone) glucagon-like peptide 1 (GLP-1) that is used as a long-acting glucagon-like […]. ...
The relative or absolute lack of insulin is responsible for diabetes. In type 1 diabetes, β-cell loss is due in most cases to an autoimmune reaction, but not exclusively (1). In type 2 diabetes (T2D), increased peripheral insulin resistance challenges the functional β-cell mass; after an initial attempt at overriding the increased insulin demand, the number of cells that produce insulin declines progressively.. Glucose entry into cells is regulated by insulin, whose secretion from β-cells is tightly coordinated by different secretagogues. Insulin secretion is initiated by the cholinergic parasympathetic stimulation of β-cells (the so-called cephalic phase) and subsequently potentiated during the enteric absorptive phase (2). In response to mechanical and chemical stimulation along the digestive tract, the intestinal incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) potentiate insulin secretion directly and indirectly, through neuronal stimulation (the ...
Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development. ...
Cardiovascular (CV) disease is the leading cause of death and morbidity in patients with type 2 diabetes. Five CV risk factors (blood pressure, resting heart rate [HR], body weight, cholesterol levels and blood glucose) are monitored routinely as safety and efficacy endpoints in randomised clinical trials for diabetes therapies. To determine if different glucagon-like peptide-1 receptor agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16 head-to-head trials directly comparing GLP-1RAs that included at least one of the five factors. Few trials reported statistical differences between GLP-1RAs in terms of systolic blood pressure (SBP), body weight and total cholesterol. Liraglutide increased heart rate versus its comparators in three separate trials. All GLP-1RAs reduced glycated haemoglobin (HbA1c), but exenatide twice daily and lixisenatide had statistically smaller effects compared with other GLP-1RAs. These descriptive data indicate that individual GLP-1RAs affect ...
Victoza®, the first once-daily human glucagon-like peptide-1 (GLP-1) analogue that regulates blood sugar in a glucose-dependent manner, is now available for people with type 2 diabetes in the UK.
[49 Pages Report] Check for Discount on Glucagon-Like Peptide 2 Receptor (GLP-2 Receptor or GLP2R) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Glucagon-Like Peptide 2...
In the insulin-secreting beta-cell line beta TC3, stimulation with 11.2 mmol/l glucose caused a rise in the intracellular free Ca2+ concentration ([Ca2+]i) in only 18% of the tested cells. The number of glucose-responsive cells increased after pretreatment of the cells with glucagon-like peptide I (GLP-I)(7-36)amide and at 10(-11) mol/l; 84% of the cells responded to glucose with a rise in [Ca2+]i. GLP-I(7-36)amide induces a rapid increase in [Ca2+]i only in cells exposed to elevated glucose concentrations (| or = 5.6 mmol/l). The action of GLP-I(7-36)amide and forskolin involved a 10-fold increase in cytoplasmic cAMP concentration and was mediated by activation of protein kinase A. It was not associated with an effect on the membrane potential but required some (small) initial entry of Ca2+ through voltage-dependent L-type Ca2+ channels, which then produced a further increase in [Ca2+]i by mobilization from intracellular stores. The latter effect reflected Ca(2+)-induced Ca2+ release and was blocked by
This trial is comparing the efficacy, tolerability and quality of life effects of liraglutide and glimepiride in patients with heart failure and type 2 diabetes
Gault, Victor and Lennox, R. and Porter, David and Holscher, Christian and Flatt, Peter (2013) Beneficial actions of glucagon-like peptide 1 (GLP-1) on hippocampal synaptic plasticity, gene expression, oxidative stress and inflammation in mice with diet-induced obesity and insulin resistance. Diabetic Medicine, 30 (Supple). p. 4. ISSN 0742-3071 Full text not available from this repository ...
Although many providers and some patients know about the potential risks of pancreatic or thyroid cancer with use of glucagon-like peptide-1 (GLP-1) receptor agonists,1 2 3 risk of breast cancer has also recently arisen as a potential risk with these drugs. The US Federal Drug Administration (FDA) and European Medicines Agency separately conducted pooled analyses of four weight management trials that investigated the use of 3.0 mg liraglutide (a type of GLP-1 receptor agonist).4 5 In these pooled analyses, 12 (0.29%) breast cancer events were reported in the liraglutide arms versus two (0.08%) events in the placebo arms.. Given the rare occurrence of these events, it was unclear whether this difference was due to chance alone or a true increase in breast cancer risk. The LEADER trial (liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results) compared liraglutide at a lower dose of … ...
OBJECTIVEPatients with the metabolic syndrome (MetS) have impaired insulin-induced enhancement of vasodilator responses. The incretin hormone glucagon-like peptide 1 (GLP-1), beyond its effects on blood glucose, has beneficial actions on vascular function. This study, therefore, aimed to assess whet
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(HealthDay) -- Drinking a diet soda before a glucose load is associated with increased glucagon-like peptide 1 (GLP-1) secretion in individuals with type 1 diabetes and healthy controls, but not in those with type 2 diabetes, ...
99658-04-5 - Glucagon-like peptide 1 (1-36)amide - Searchable synonyms, formulas, resource links, and other chemical information.
TY - JOUR. T1 - Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects. T2 - A pilot study. AU - Sathananthan, Airani. AU - Dalla Man, Chiara. AU - Micheletto, Francesco. AU - Zinsmeister, Alan R.. AU - Camilleri, Michael. AU - Giesler, Paula D.. AU - Laugen, Jeanette M.. AU - Toffolo, Gianna. AU - Rizza, Robert A.. AU - Cobelli, Claudio. AU - Vella, Adrian. PY - 2010/9. Y1 - 2010/9. N2 - OBJECTIVE - Glucagon-like peptide (GLP)-1 receptor is encoded by GLP1R. The effect of genetic variation at this locus on the response to GLP-1 is unknown. This study assessed the effect of GLP1R polymorphisms on insulin secretion in response to hyperglycemia and to infused GLP-1 in nondiabetic subjects. RESEARCH DESIGN AND METHODS - Eighty-eight healthy individuals (aged 26.3 ± 0.6 years, fasting glucose 4.83 ± 0.04 mmol/l) were studied using a hyperglycemic clamp. GLP-1 was infused for the last 2 h of the study (0.75 pmol/kg/min over 121-180 min, 1.5 ...
Liraglutide will be prescribed and titrated by the treating physician and will be self-administered by the subject s.c. (under the skin) once daily. Study participants being treated with GLP-1 (Glucagon-Like Peptide 1)agonists or DDP-4-inhibitors (Dipeptidyl-peptidase 4 ) should stop treatment when initiating liraglutide treatment ...
Liraglutide will be prescribed and titrated by the treating physician and will be self-administered by the subject s.c. (under the skin) once daily. Study participants being treated with GLP-1 (Glucagon-Like Peptide 1)agonists or DDP-4-inhibitors (Dipeptidyl-peptidase 4 ) should stop treatment when initiating liraglutide treatment ...
Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial - Volume 116 Issue 2 - Jeanne H. Bottin, Jonathan R. Swann, Eleanor Cropp, Edward S. Chambers, Heather E. Ford, Mohammed A. Ghatei, Gary S. Frost
The gut hormone, glucagon-like peptide-1 (GLP-1) is a potent insulin secretogogue with potential as a therapy for non-insulin-dependent diabetes mellitus (NIDDM). GLP-1 has been shown to reduce glucose concentrations, both basally, and, independently, in response to a single meal. For it to be an ef …
Albiglutide (trade names Eperzan in Europe and Tanzeum in the US) is a glucagon-like peptide-1 agonist (GLP-1 agonist) drug marketed by GlaxoSmithKline (GSK) for treatment of type 2 diabetes. As of 2017 it is unclear if it affects a persons risk of death. GSK has announced that it intends to withdraw the drug from the worldwide market by July 2018 for economic reasons. Albiglutide is used for the treatment of type 2 diabetes in adults. It can be used alone (if metformin therapy is ineffective or not tolerated) or in combination with other antidiabetic drugs, including insulins. According to a 2015 analysis, albiglutide is less effective than other GLP-1 agonists for lowering glycated hemoglobin (HbA1c, an indicator for long-term blood glucose control) and weight loss. It also seems to have fewer side effects than most other drugs of this class, except for reactions at the injection site which are more common under albiglutide than, for example, under liraglutide. The US approval lists the ...
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article{1ab52f88-4d01-45dd-a399-2e230c289278, abstract = {High-resolution capacitance measurements were used to explore the effects of the gut hormones GLP-I(7-36) amide [glucagon-like peptide I(7-36) amide] and GIP (glucose-dependent insulinotropic polypeptide) on Ca2+-dependent exocytosis in glucagon-secreting rat pancreatic alpha-cells. Both peptides produced a greater than threefold potentiation of secretion evoked by voltage-clamp depolarizations, an effect that was associated with an approximately 35% increase of the Ca2+ current. The stimulatory actions of GLP-I(7-36) amide and GIP were mimicked by forskolin and antagonized by the protein kinase A (PKA)-inhibitor Rp-8-Br-cAMPS. The islet hormone somatostatin inhibited the stimulatory action of GLP-I(7-36) amide and GIP via a cyclic AMP-independent mechanism, whereas insulin had no effect on exocytosis. These data suggest that the alpha-cells are equipped with receptors for GLP-I and GIP and that these peptides, in addition to their ...
Background: In humans, there is a significant decrease in myocardial contractile function post arrest evidenced by decreased cardiac output and ejection fraction. This decreased function is also associated with impaired myocardial microcirculatory function in swine. In ischemic models, the endogenous incretin hormone glucagon-like peptide-1 (GLP-1) has demonstrated benefits in myocardial infarct size reduction and improvement of left ventricular (LV) function, however treatment with this agent has not been evaluated following resuscitation from cardiac arrest. We hypothesized that post resuscitation administration of GLP-1 would improve myocardial microcirculatory function.. Methods: Domestic swine (n=20; 30-35 kg) were electrically fibrillated and left untreated for 8 minutes. Aggressive ACLS was performed to restore spontaneous circulation. Animals were then blindly randomized to post resuscitation infusions of either human rGLP-1 (American Peptide, 10 pM/kg/min) or equal volume saline for 4 ...
TY - JOUR. T1 - N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity. AU - Green, BD. AU - Mooney, MH. AU - Gault, Victor. AU - Irwin, Nigel. AU - Bailey, CJ. AU - Harriott, P. AU - Greer, B. AU - OHarte, Finbarr. AU - Flatt, Peter. PY - 2004/3. Y1 - 2004/3. N2 - Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid in-activation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1 (9-36),amide, while ...
The FDA needs a number of post-marketing studies of Invokana, including a cardiovascular outcomes trial to look for photosensitivity, liver abnormalities, malignancies, serious pancreatitis, adverse pregnancy outcomes, and severe hypersensitivity reactions. Other post-marketing studies include one for bone safety and two on children. Nesina (alogliptin), Oseni (alogliptin and pioglitazone), and Kazano (alogliptin and metformin hydrochloride) were approved in January 2013. Alogliptin, a type of DPP-4i, is the new kid on the block, while pioglitazone and metformin have had FDA approval for years. Alogliptin tablets, along with other DPP-4 inhibitors, slow down the inactivation of incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The bottom line is, DPP-4 inhibitors helps stimulate the release of insulin after eating, ultimately resulting in better control of blood sugar levels.. The most common side effects of alogliptin were found to be ...
Middle East & Africa (United Arab Emirates, Saudi Arabia, South Africa, etc). Glucagon like peptide-1 (GLP-1) agonists Product/Service Development. Knowing how the product/services fit the needs of clients and what changes would require to make the product more attractive is the need of an hour. Useful approaches to focus group by utilizing User Testing and User Experience Research. Demand-side analysis always helps to correlate consumer preferences with innovation.. Marketing Communication and Sales Channel. Understanding marketing effectiveness on a continual basis help determine the potential of advertising and marketing communications and allow us to use best practices to utilize an untapped audience. In order to make marketers make effective strategies and identify why the target market is not giving attention, we ensure the Study is Segmented with appropriate marketing & sales channels to identify potential market size by Revenue and Volume* (if Applicable).. Pricing and ...
TY - JOUR. T1 - Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans. AU - Snyder, Eric M.. AU - Carr, Richard D.. AU - Deacon, Carolyn F.. AU - Johnson, Bruce David. PY - 2008/10. Y1 - 2008/10. N2 - Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 ...
TY - JOUR. T1 - Vagally mediated effects of glucagon-like peptide 1. T2 - In vitro and in vivo gastric actions. AU - Holmes, Gregory M.. AU - Browning, Kirsteen N.. AU - Tong, Melissa. AU - Qualls-Creekmore, Emily. AU - Travagli, R. Alberto. PY - 2009/10/1. Y1 - 2009/10/1. N2 - Glucagon-like peptide-1 (GLP-1) is a neuropeptide released following meal ingestion that, among other effects, decreases gastric tone and motility. The central targets and mechanism of action of GLP-1 on gastric neurocircuits have not, however, been fully investigated. A high density of GLP-1 containing neurones and receptors are present in brainstem vagal circuits, suggesting that the gastroinhibition may be vagally mediated. We aimed to investigate: (1) the response of identified gastric-projecting neurones of the dorsal motor nucleus of the vagus (DMV) to GLP-1 and its analogues; (2) the effects of brainstem application of GLP-1 on gastric tone; and (3) the vagal pathway utilized by GLP-1 to induce gastroinhibition. We ...
OBJECTIVE: The aim of the present study was to investigate whether 4 weeks of near-normalization of blood glucose (BG) improves incretin hormone secretion and pancreatic B-cell function during a mixed meal.. RESEARCH DESIGN AND METHODS: Nine patients with Type 2 diabetes in poor glycaemic control [glycated haemoglobin (HbA(1c)) 8.0 +/- 0.4%] were investigated before and after 4 weeks of near-normalization of BG (mean BG 6.4 +/- 0.3 mmol/l) using insulin treatment. HbA(1c) after insulin treatment was 6.6 +/- 0.3%. For comparison, nine healthy control subjects were also studied. Postprandial glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) incremental responses were assessed during a mixed meal test. Fasting and postprandial pancreatic B-cell function was determined from calculations of insulin secretion rates in relation to plasma glucose.. RESULTS: There was no difference in IAUC(totalGLP-1) or in IAUC(totalGIP) between the two experimental days. B-cell ...
An incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to lower plasma glucose via glucose-dependent insulin secretion and to reduce appetite. We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats. This finding suggested that the combination treatment might produce a greater antidiabetic and anorectic effect, based on enhanced GLP-1 action. In this study, we assessed the effects of subchronic treatment with metformin and a DPPIV inhibitor, valine-pyrrolidide (val-pyr), on glycemic control, food intake, and weight gain using Zucker fa/fa rats, a model of obesity and impaired glucose tolerance. The combination treatment caused a significant increase of GLP-1 level in Zucker fa/fa rats. In a subchronic study, val-pyr, metformin, or both compounds were administered orally b.i.d. for 14 days. The combination treatment significantly ...
Glucagon-like peptide-1 (GLP-1) originates from the gastrointestinal system in response to the presence of nutrition in the intestinal lumen and potentiates postprandial insulin secretion. Also, it acts as an immune-modulator which has influences on cell-mediated immunity. The aim of this study was to determine the impact of early enteral nutrition versus late enteral nutrition on plasma GLP-1 levels and the relationship between GLP-1 changes and cell-mediated immunity. The study was designed as a prospective, single-blinded study and carried out in the neurology intensive care unit (ICU) of a university hospital. Twenty-four naive patients with acute thromboembolic cerebrovascular events, with National Institute of Health (NIH) stroke scores between 12 and 16, were included. Any condition interfering with GLP-1 and immunity was regarded as exclusion criterion. Two patients died, and two dropped out of the study due to complicating conditions. Patients were randomly subjected to early enteral feeding
Glutamine-evoked cAMPi responses in GLUTag cells. GLUTag cells were transfected with the cAMP probe, Epac2 camps. FRET was measured as the YFP/CFP ratio by exci
Glucagon-like peptide-1 (GLP-1), an insulinotropic and glucoincretin hormone, is a potentially important therapeutic agent in the treatment of diabetes. We previously provided evidence that GLP-1 induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent manner. In the present study, we investigated the downstream effectors of PI-3K to determine the precise signal transduction pathways that mediate the action of GLP-1 on beta-cell proliferation. GLP-1 increased extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. GLP-1 also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta isoform in INS as well as in dissociated normal rat beta-cells as shown by immunolocalization and Western immunoblotting analysis. Tritiated thymidine incorporation measurements showed that the p38 MAPK inhibitor SB203580
Peptide-based drugs are highly effective medicines with relatively short duration of action and of variable therapeutic index. Glucagon-like peptide 1 is a hormone that offers promise in the treatment of Type II diabetes. However, the biggest problem in the therapeutic use of GLP-1 is its extremely short half-life in plasma (~2 min). A prodrug of GLP-1 should extend and improve the pharmacodynamics of this peptide hormone. We have designed prodrugs that slowly convert to the parent drug at physiological conditions of 37C and pH 7.2 driven by their inherent chemical instability without the need of any enzymatic cleavage. We observed that amide prodrugs could not convert to the active peptides under physiological conditions. Consequently, we decided to synthesize peptide drugs which had a hydroxy-terminal extension instead of a Nterminal amine. Ester prodrugs were prepared using these hydroxy-peptides as the scaffold. We explored the diketopiperazine and diketomorpholine (DKP and DMP) strategy for ...
Previous studies have demonstrated that glucagon-like peptide-1 (GLP-1) stimulates β-cell formation and insulin secretion. Currently, there has been no report in understanding the effect of GLP-1 / its agonist exendin-4 in differentiation of human embryonic stem cells (hESCs) to definitive endodermal (DE). We hypothesized that exendin-4 signaling in hESCs via GLP-1 receptor (GLP-1R) may have potential role in DE differentiation. The effect of Ex-4 on pluripotent hESCs and the combined effect of Ex-4 and activin A-treated hESC-derived DE were examined. Analysis by quantitative real-time PCR (qPCR) demonstrates that Ex-4 alone was not sufficient to enhance DE formation in hESCs. On the other hand, a combinatorial treatment with activin A and Ex-4 resulted in significant decrease in expression levels of DE markers. The miRNA expression profiles between activin A-treated hESCs and activin A/Ex-4-treated hESCs after 5 days of treatment demonstrated similar expression levels of endoderm and ...
Contour will contribute a new usage paradigm using adaptive activities and intelligent recommendations. The aim is to create a context-sensitive user interface that adapts to current context, current activities and behavioral patterns of the user. The overall goal is to create a data-centric user interface which is not concerned with applications but rather offers intelligently combined data through a context-sensitive recommendation manager. Contour is part of Plasma Active, the new user experience for all kind of devices like Tablets, Smartphones, in-car or Set Top Boxes. Plasma Active uses existing free desktop technology and brings it to a spectrum of devices through a desirable and innovative user interface. Contour and Plasma Active are currently at a conceptual stage. We have a proof-of-concept working on certain hardware, with a basic working shell, but an incomplete set of key applications. We welcome people to take part in this endeavor to make Contour and Plasma Active rock. ...
Contour will contribute a new usage paradigm using adaptive activities and intelligent recommendations. The aim is to create a context-sensitive user interface that adapts to current context, current activities and behavioral patterns of the user. The overall goal is to create a data-centric user interface which is not concerned with applications but rather offers intelligently combined data through a context-sensitive recommendation manager. Contour is part of Plasma Active, the new user experience for all kind of devices like Tablets, Smartphones, in-car or Set Top Boxes. Plasma Active uses existing free desktop technology and brings it to a spectrum of devices through a desirable and innovative user interface. Contour and Plasma Active are currently at a conceptual stage. We have a proof-of-concept working on certain hardware, with a basic working shell, but an incomplete set of key applications. We welcome people to take part in this endeavor to make Contour and Plasma Active rock. ...
Glucagon-like peptide-1 (GLP-1) receptor agonists certainly are a class of injective anti-diabetic drugs that improve glycemic control and several various other atherosclerosis-related parameters in individuals with type 2 diabetes (T2D). threat of hypoglycemic shows. Alternatively, several case reviews have linked the usage of these medications, generally exenatide, using the incident of severe kidney injury, mainly through hemodynamic derangement because of nausea, throwing up, and diarrhea. The most frequent symptoms from the usage of GLP-1 receptor agonists are gastrointestinal symptoms, generally nausea. Various other common undesireable effects consist of shot site reactions, headaches, and nasopharyngitis, but these results do not generally bring about discontinuation from the medication. Current evidence implies that GLP-1 receptor agonists havent any negative effects over the cardiovascular threat of sufferers with T2D. Hence, GLP-1 receptor agonists may actually have a good basic ...
FDA has approved semaglutide (Ozempic—Novo Nordisk) as an adjunct to diet and exercise for the treatment of type 2 diabetes in adults. The drug, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, was approved in 0.5-mg and 1.0-mg doses, to be administered once a week with a dedicated prefilled pen device ...
It was first reported in 1964 that there was greater and more sustained insulin release in response to an oral glucose load when compared with the same glucose load given intravenously.1 With the discovery of an incretin hormone known as glucose-dependent insulinotropic polypeptide (GIP), this enhanced release of insulin in response to ingestion of glucose became known as the incretin effect.2 In 1986, Nauck et al showed that despite similar levels of GIP in response to an oral glucose load, patients with type 2 diabetes (T2D) had an impaired incretin effect.3 Shortly after this, glucagon-like peptide 1 (GLP-1) was discovered in 1987 and was found to be more effective than GIP in stimulating insulin and reducing peak plasma glucose concentrations.4 GLP-1 was initially thought to primarily affect insulin release; however, it has been found to exert many other effects in glucose metabolism. GLP-1 is released from the distal ileum and colon within minutes of a meal and, while it does enhance ...
To address the neural mediation of the eating-inhibitory effect of circulating glucagon-like peptide-1 (GLP-1), we investigated the effects of 1) intra-fourth ventricular infusion of the GLP-1 receptor antagonist exendin-9 or 2) area postrema lesion on the eating-inhibitory effect of intrameal hepatic portal vein (HPV) GLP-1 infusion in adult male rats. To evaluate the physiological relevance of the observed effect we examined 3) the influence of GLP-1 on flavor acceptance in a 2-bottle conditioned flavor avoidance test, and 4) measured active GLP-1 in the HPV and vena cava (VC) in relation to a meal and in the VC after HPV GLP-1 infusion. Intrameal HPV GLP-1 infusion (1 nmol/kg body weight-5 min) specifically reduced ongoing meal size by almost 40% (P , .05). Intra-fourth ventricular exendin-9 (10 μg/rat) itself did not affect eating, but attenuated (P , .05) the satiating effect of HPV GLP-1. Area postrema lesion also blocked (P , .05) the eating-inhibitory effect of HPV GLP-1. Pairing ...
Over the past century, considerable progress has been made in understanding the role of enteroendocrine signals in regulating glucose. One substantial advance was the delineation of the the incretin effect, which refers to the ability of orally administered glucose to stimulate pancreatic insulin secretion to a greater extent than glucose administered intravenously.1 Glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide are the two key enteroendocrine factors responsible for the incretin effect.2 GLP-1, secreted from the lower gastrointestinal tract L-cells after nutrient ingestion, stimulates endogenous insulin secretion in a glucose dependent manner, inhibits postprandial glucagon release, delays gastric emptying, and increases satiety.3 However, GLP-1 is of limited therapeutic use because it is rapidly degraded by dipeptidyl peptidase 4, an enzyme produced at epithelial and endothelial membranes. In the linked systematic review and meta-analysis ...
A lot of new medicines have come out, with a pile of new acronyms: GLP-1, DPP-4, BYOB…well, that last one is probably familiar, but a little background on the other two might not be out of place. Youre going to be seeing a lot more of them in the future, and itll help to be on speaking terms.. First of all, what is an incretin, anyway? An incretin is a hormone released from cells in the gut in response to eating food. Incretins were discovered when scientists noticed that people secreted more insulin after actually eating glucose than after being given a comparable amount of glucose intravenously. They knew there had to be a trigger for that extra insulin secretion, and the trigger was incretin.. Gulp-1, A Gutsy Incretin. The star incretin in diabetes treatment, and our hero in this little tale, is glucagon-like peptide-1, or GLP-1. After a meal, the gut secretes GLP-1 in response to the arrival of food from the stomach. GLP-1 then does several good things to lower blood sugar. It binds to ...
RESULTS Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P , 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P , 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose. ...
The story of incretins is an exception to the general rule that there are 20 or more years from basic research to clinical practice. In a study published in 1906 titled, On the Treatment of Diabetes Mellitus by Acid Extract of Duodenal Mucous Membrane, Moore1 stated, [T]he internal secretion of the pancreas might be stimulated and initiated … by a substance of the nature of a hormone or secretin yielded by the duodenal mucous membrane. In 1932, LaBarre2 investigated the effects of gut-derived factors on insulin secretion, calling these factors incretins. By the 1960s, most researchers accepted the idea that incretins play a role in controlling insulin secretion, although the clinical relevance of these substances remained undefined. Understanding the importance of these basic science observations awaited the seminal work of Nauck et al,3 who, in 1986, demonstrated that the effects of incretins were reduced in individuals with type 2 diabetes mellitus (T2DM).3 That report provided a ...
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human β cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes ...
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human β cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes ...
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human β cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes ...
This phase I, placebo-controlled, randomized, double-blind, two-period, crossover study assessed the pharmacodynamics of liraglutide following a high-fat meal
Introduction: Liraglutide and Exenatide are used in adults who are affected by type-2 diabetes to control their blood glucose level. They are administered by the patients by subcutaneous injection, Liraglutide once a day while Exenatide twice a day. The aim of this study was to evaluate medication adherence and persistence of treatment with Liraglutide and Exenatide with a new strategy of calculation also giving economic evaluations on therapy costs for Received Daily Dose. Materials and Methods: In this retrospective study, we took into account 16 months from 1st September 2011 to 31st December 2012. Treatment adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence is calculated into account the actual therapy days, comparing posology with supplied dose and the graph is drawn using Kaplan-Meir method. Results: The number of patients studied for Liraglutide was 114 and 220 and 58 and 60 for Exenatide respectively in 2011 and 2012. Adherence to therapy,
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EMMX proudly develops novel molecules and reagents to drug discovery and cancer research. We are scientists driven by a devotion to discovery and innovation, and we work hard every day to find new ways to streamline life science research.. ...
EMMX proudly develops novel molecules and reagents to drug discovery and cancer research. We are scientists driven by a devotion to discovery and innovation, and we work hard every day to find new ways to streamline life science research.. ...
In this weeks Nature Medicine, researchers reveal that glucagon-like peptide-1 (GLP-1), a product of proglucagon processing, may have an important role in learning and neuroprotection.. The peptide, first found in intestinal L cells of the gut, is also expressed in the brain, along with its receptor (GLP-1R). This prompted principal investigator Colin Haile, Jefferson Medical College, Philadelphia, to investigate the role of GLP-1 in neurons. Working with an international group of collaborators, Haile and first author Matthew During looked for potential neurologic roles for the peptide. When they administered it to rats, the authors found that the animals performed better than controls in a variety of learning tasks. In the Morris water maze, for example, rats directly injected in the brain with 0.1 micrograms of GLP-1 traveled much shorter distances (about two meters on average) than untreated littermates (about 10 meters) in search of the hidden platform.. To further investigate the role of ...
Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low density lipoprotein in HN Thx. Unexpectedly, however, Thx reduced serum and hepatic triglyceride concentrations. Further studies revealed that Thx dramatically increased circulating GLP-1 as well as increased expressions of GLP-1 in small intestine. Diminished hepatic expressions of lipogenic genes, were observed in HN Thx group. Beta-catenin and glutamine synthetase, a known target of beta-catenin, ...