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Glucagon-like peptide

Bronwen J Mayo, Andrea M Stringer, Joanne M Bowen, Emma H Bateman, Dorothy M Keefe
PURPOSE: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention...
October 21, 2016: Cancer Chemotherapy and Pharmacology
Katherine R Tuttle, T Dwight McKinney, Jaime A Davidson, Greg Anglin, Kristine D Harper, Fady T Botros
Dulaglutide (DU) is a once-weekly glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes. Integrated data from 9 phase 2 and 3 trials in type 2 diabetes (N = 6005) were used to evaluate effects of DU on estimated glomerular filtration rate (eGFR, mL/min/1.73m(2) [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR, mg/g), and kidney adverse events. No significant differences in eGFR were observed during treatment for DU versus placebo (PL), active comparators (AC), or insulin glargine (IG) (mean±SD; DU: 87...
October 21, 2016: Diabetes, Obesity & Metabolism
Susan L Samson, Alan J Garber
Incretin-based therapies are important addition to our armamentarium for the treatment of type 2 diabetes (T2DM). There are six Glucagon-like peptide-1 receptor agonists (GLP-1RAs) which have received regulatory approval for clinical use. The short-acting GLP-1RAs include exenatide twice daily, liraglutide once daily, and lixisenatide once daily. The approved long-acting GLP-1RAs are administered weekly and are exenatide, albiglutide, and dulaglutide. Although all of these therapies lower hemoglobin A1C (HbA1C), there also are unique features of GLP-1RAs that have been made manifest from clinical trial data with regard to weight-loss efficacy, fasting and post-prandial glucose control, cardiovascular safety and protection, and gastrointestinal and injection adverse effects...
December 2016: Current Diabetes Reports
Geisa Nogueira Salles, Fernanda Aparecida Dos Santos Pereira, Cristina Pacheco-Soares, Fernanda Roberta Marciano, Christian Hölscher, Thomas J Webster, Anderson Oliveira Lobo
Bioresorbable electrospun fibres have highly functional features that can preserve drug efficacy, avoiding premature degradation, and control drug release rates over long periods. In parallel, it is known that Alzheimer's disease (AD) has been linked to impaired insulin signalling in the brain. Glucagon-like peptide 1 (GLP-1) analogues have beneficial effects on insulin release and possess exceptional neuroprotective properties. Herein, we describe for the first time the incorporation of a GLP-1 analogue, liraglutide, into electrospun poly (lactic acid) (PLA) fibres with in situ gelatin capsules, in order to provide the controlled release of liraglutide, improving neuroprotective properties...
October 20, 2016: Molecular Neurobiology
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Deju Peng, Huiqin Ma, Shangwu Chen
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, is an excellent therapeutic peptide drug for type 2 diabetes due to longer lasting biological activity compared to GLP-1. This study explored the feasibility of using probiotic Lactobacillus paracasei as an oral vector for recombinant exendin-4 peptide delivery, an alternative to costly chemical synthesis and inconvenient administration by injection. L. paracasei transformed with a plasmid encoding the exendin-4 gene (L. paracasei L14/pMG76e-exendin-4) with a constitutive promotor was successfully constructed and showed efficient secretion of exendin-4...
2016: PloS One
Fabio Broglio, Edoardo Mannucci, Raffaele Napoli, Antonio Nicolucci, Francesco Purrello, Elena Nikonova, William Stager, Roberto Trevisan
AIMS: To evaluate long term efficacy and safety of lixisenatide, a short-acting, prandial GLP-1 RA (Glucagon-Like Peptide-1 Receptor Agonists) as add-on therapy in type 2 diabetes mellitus. METHODS: A meta-analysis of 76-week results of five placebo-controlled clinical trials from the GetGoal program was performed including 3,000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea ± metformin (GetGoal-S), basal insulin ± metformin (GetGoal-L) or pioglitazone ± metformin (GetGoal-P)...
October 20, 2016: Diabetes, Obesity & Metabolism
Tongzhi Wu, Cong Xie, Hang Wu, Karen L Jones, Michael Horowitz, Christopher K Rayner
In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 (GLP-1) secretion. We evaluated the effects of metformin on serum 3-O-methylglucose (3-OMG, a marker of glucose absorption) and plasma total GLP-1 concentrations during a standardised intraduodenal infusion of glucose and 3-OMG in patients with type 2 diabetes. 12 patients, treated with metformin 850 mg bd or placebo each for 7 days in a double-blind, randomised, crossover design (14 days 'washout' between treatments), were evaluated on days 5 or 8 of each treatment (6 each)...
October 20, 2016: Diabetes, Obesity & Metabolism
Gunter Laux, Sarah Berger, Joachim Szecsenyi, Petra Kaufmann-Kolle, Rüdiger Leutgeb
BACKGROUND: The objective of this study was to analyze prescription decisions for family practice (FP) patients with Diabetes mellitus type 2 (DM2) using the case of the incretin mimetics Dipeptidyl peptidase-4 (DDP-4) inhibitors and Glucagon-like peptide-1 (GLP-1) agonists dependent on patients' health insurance status (statutory or private) in Germany. This study is important since the scientific debate is still open with regard to DPP-4-inhibitors and GLP-1-agonists, where some critics are raising questions on potential long-term risks for patients...
October 19, 2016: BMC Family Practice
J J Castro, S Y Morrison, A Hosseinni, J J Loor, J K Drackley, I R Ipharraguerre
No abstract text is available yet for this article.
November 2016: Journal of Dairy Science
G S M Paula, L L Souza, N O S Bressane, R Maravalhas, M Wilieman, T Bento-Bernardes, K R Silva, L S Mendonca, K J Oliveira, C C Pazos-Moura
Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48...
October 18, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Bernt Johan von Scholten, Frederik Persson, Signe Rosenlund, Peter Hovind, Jens Faber, Tine Willum Hansen, Peter Rossing
AIMS: Patients with type 2 diabetes and albuminuria have high cardiorenal morbidity and mortality despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. MATERIALS AND METHODS: Randomised, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1...
October 17, 2016: Diabetes, Obesity & Metabolism
Giulia Cantini, Alessandra Di Franco, Edoardo Mannucci, Michaela Luconi
Glucagon-like peptide 1(9-36) [GLP-1(9-36)] is generated by dipeptidyl peptidase-4 (DPP4) cleavage of the gut incretin hormone, GLP-1(7-36). Since GLP-1(9-36) has a very low affinity for the GLP-1 receptor (GLP-1R), it has so far been considered an inactive form of GLP-1. Here we show GLP-1(9-36) activity in human adipose stem cells (ASC) in vitro. GLP-1(9-36) inhibits human ASC proliferation, glucose uptake and adipogenesis, as well as induces cell apoptosis, to a similar extent as GLP-1(7-36) and liraglutide...
October 13, 2016: Molecular and Cellular Endocrinology
Tongzhi Wu, Christopher K Rayner, Michael Horowitz
The GI tract is central to the regulation of postprandial glycemia, with the rate of gastric emptying and the secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, being key determinants. Gastric emptying exhibits a large interindividual variation; the latter not only accounts for differences in postprandial glycemia but also determines postprandial incretin profiles. Accordingly, the rate of gastric emptying may affect the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors...
October 13, 2016: Biomarkers in Medicine
Parjeet Kaur, Shama Mahendru, Ambrish Mithal
BACKGROUND: Long-term efficacy of liraglutide, a glucagon-like peptide-1 analog, on body weight and glycemic control has not been studied in Indian Type 2 diabetes mellitus (T2DM) subjects. AIM: To evaluate the effect of liraglutide on glycemic control and body weight for 1 year in Indian T2DM patients. METHODS: Liraglutide was prescribed to 96 obese patients with T2DM and followed up for 1 year. Clinical parameters were measured at baseline and 3, 6, 9, and 12 months...
September 2016: Indian Journal of Endocrinology and Metabolism
Marie K Holt, Stefan Trapp
Glucagon-like peptide-1 (GLP-1) within the brain is a potent regulator of food intake and most studies have investigated the anorexic effects of central GLP-1. A range of brain regions have now been found to be involved in GLP-1 mediated anorexia, including some which are not traditionally associated with appetite regulation. However, a change in food intake can be indicative of not only reduced energy demand, but also changes in the organism's motivation to eat following stressful stimuli. In fact, acute stress is well-known to reduce food intake...
December 31, 2016: Cogent Biology
Rodrigo B Mansur, Juhie Ahmed, Danielle S Cha, Hanna O Woldeyohannes, Mehala Subramaniapillai, Julie Lovshin, Jung G Lee, Jae-Hon Lee, Elisa Brietzke, Eva Z Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas Hajek, Roger S McIntyre
BACKGROUND: There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder. METHODS: In this 4-week, pilot, open-label, domain-based study (e...
October 1, 2016: Journal of Affective Disorders
Yusuke Nakao, Michiko Horiguchi, Ryuji Nakamura, Sachie Sasaki-Hamada, Chihiro Ozawa, Taichi Funane, Ryo Ozawa, Jun-Ichiro Oka, Chikamasa Yamashita
Depression is a common mental disorder. More than 350 million people of all ages suffer from depression worldwide. Although a number of antidepressants are available, >20% of patients with major depressive disorder suffer from treatment-resistant depression. Therefore, development of novel therapeutics to overcome this condition is required. We reported that intracerebroventricular administration of glucagon-like peptide-2 (GLP-2) exerts antidepressant-like effects treated with or without adrenocorticotropic hormone...
October 5, 2016: International Journal of Pharmaceutics
Pelle L Ishøy, Filip K Knop, Brian V Broberg, Nikolaj Bak, Ulrik B Andersen, Niklas R Jørgensen, Jens J Holst, Birte Y Glenthøj, Bjørn H Ebdrup
AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia...
September 26, 2016: Diabetes, Obesity & Metabolism
M S Abd El Aziz, M Kahle, J J Meier, M A Nauck
AIMS: To study differences in clinical outcomes between initiating glucagon-like peptide-1 receptor agonist (GLP-1 RAs) vs. insulin treatment in patients with type 2 diabetes treated with oral glucose-lowering medications (OGLM). METHODS: Prospective, randomized trials comparing GLP-1 RA and insulin treatment head-to-head as add-on to OGLM were identified (PubMed). Differences from baseline values were compared for HbA1c , fasting plasma glucose, body weight, blood pressure, heart rate and lipoproteins...
October 7, 2016: Diabetes, Obesity & Metabolism
Na Wang, Jin-Ping Zhang, Xiao-Yan Xing, Zhao-Jun Yang, Bo Zhang, Xin Wang, Wen-Ying Yang
BACKGROUND: This post-hoc analysis investigated whether changes in endogenous glucagon-like peptide-1 (GLP-1) levels were associated with weight loss in newly diagnosed diabetes patients. METHODS: Seven hundred eighty-four subjects from the MARCH (Metformin and AcaRbose in Chinese as initial Hypoglycemic treatment) study were stratified by changes in GLP-1 levels (∆GLP-1). Changes in clinical and physiological parameters were evaluated across ∆GLP-1 subgroups to assess correlations between ∆GLP-1 and weight loss in acarbose vs...
September 22, 2016: Journal of Diabetes
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