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Glucagon AND Review

Donatella Paola Provvisiero, Claudia Pivonello, Giovanna Muscogiuri, Mariarosaria Negri, Cristina de Angelis, Chiara Simeoli, Rosario Pivonello, Annamaria Colao
Bisphenol A (BPA) is an organic synthetic compound employed to produce plastics and epoxy resins. It is used as a structural component in polycarbonate beverage bottles and as coating for metal surface in food containers and packaging. The adverse effects of BPA on human health are widely disputed. BPA has been recently associated with a wide variety of medical disorders and, in particular, it was identified as potential endocrine-disrupting compound with diabetogenic action. Most of the clinical observational studies in humans reveal a positive link between BPA exposure, evaluated by the measurement of urinary BPA levels, and the risk of developing type 2 diabetes mellitus...
October 6, 2016: International Journal of Environmental Research and Public Health
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
October 25, 2016: Expert Opinion on Drug Metabolism & Toxicology
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
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor...
October 2016: Diabetes & Metabolism Journal
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
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
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
Sonal Singh, Eugene E Wright, Anita Ym Kwan, Juliette C Thompson, Iqra A Syed, Ellen E Korol, Nathalie A Waser, Maria B Yu, Rattan Juneja
AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched...
October 7, 2016: Diabetes, Obesity & Metabolism
Antonella Tramutola, Andrea Arena, Chiara Cini, D Allan Butterfield, Eugenio Barone
Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease (AD) subjects revealed insulin resistance in the brain, suggesting a role of this condition in cognitive deficits observed in AD. In this review, we focus on the glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is collecting increasing attention because of its association with insulin signaling activation. Areas covered: The role of GLP-1-mediated effects in the brain and how they are affected along the progression of AD pathology is discussed...
October 7, 2016: Expert Review of Neurotherapeutics
Soe Naing, Anapuma Poliyedath, Stutee Khandelwal, Teresa Sigala
Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the FDA for the treatment of T2DM in the United States and other parts of the world in the last decade...
October 4, 2016: Postgraduate Medicine
Omorogieva Ojo
OBJECTIVE: This review examines the use of exenatide twice daily in managing changes in markers of cardiovascular risk in patients with type 2 diabetes. BACKGROUND: Type 2 diabetes is a progressive metabolic disorder, which results from defects in insulin secretion and/or insulin action leading to chronic hyperglycaemia and associated cardiovascular complications. Despite the use of diet, exercise, oral antihyperglycaemic agents and insulin, the progressive nature of the condition means that the levels of the preventive and treatment measures would have to be increased and/or new therapies have to be developed in order to address the long term impact of type 2 diabetes...
2016: International Journal of Environmental Research and Public Health
Claudia Harper, Andrea L Pattinson, Hamish A Fernando, Jessica Zibellini, Radhika V Seimon, Amanda Sainsbury
BACKGROUND: New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this. MATERIALS AND METHODS: This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction. RESULTS AND CONCLUSIONS: All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%-11% of pre-surgical values) and weakest for dietary restriction (1%-1...
September 26, 2016: Hormone Molecular Biology and Clinical Investigation
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
Sara Baldassano, Antonella Amato, Flavia Mulè
Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released from enteroendocrine L-type cells together with glucagon like peptide-1 in response to dietary nutrients. GLP-2 acts through a specific receptor, the GLP-2 receptor, mainly located in the gut and in the brain. Classically, GLP-2 is considered a trophic hormone involved in the maintenance of intestinal epithelial morphology and function. This role has been targeted for therapies promoting repair and adaptive growth of the intestinal mucosa...
September 21, 2016: Peptides
Ehab Mudher Mikhael
Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan...
2016: Journal of Diabetes Research
R Burcelin, P Gourdy
Over the past 30 years, there has been a dramatic rise in global obesity prevalence, resulting in significant economic and social consequences. Attempts to develop pharmacological agents to treat obesity have met with many obstacles including the lack of long-term effectiveness and the potential for adverse effects. Historically, there have been limited treatment options for overweight and obesity; however, since 2012, a number of new drugs have become available. A number of peptides produced in the gut act as key mediators of the gut-brain axis, which is involved in appetite regulation...
September 16, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
John Rafferty, Hema Nagaraj, Alice P McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr, Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T...
September 9, 2016: Current Medicinal Chemistry
Nadine Taleb, Ahmad Haidar, Virginie Messier, Véronique Gingras, Laurent Legault, Rémi Rabasa-Lhoret
The role of glucagon in the pathophysiology of diabetes has long been recognized while its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that glucagon incorporation has the potential to further decrease the hypoglycaemic risk and improve the overall glucose control. However, long term potential safety and benefits need to be investigated given its recognised systemic effects of glucagon...
September 15, 2016: Diabetes, Obesity & Metabolism
Karel Vondra
UNLABELLED: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available...
2016: Vnitr̆ní Lékar̆ství
Helene Bihan, Winda L Ng, Dianna J Magliano, Jonathan E Shaw
AIMS: To identify the determinants of efficacy of glucagon-like peptide-1 receptor agonists (GLP-1A) and dipeptidyl peptidase-4 inhibitors (DPP-4I). METHODS: MEDLINE and EMBASE were searched between 01/01/2011 and 15/08/2014 for randomized controlled trials of 12-52weeks' duration, which reported the change in glycated hemoglobin (HbA1c) from baseline as the primary end point, and reported data about predictors of efficacy of incretins. RESULTS: Among 4172 studies found, 77 studies reported data on baseline HbA1c, age, sex, ethnicity, body mass index (BMI), and history of diabetes in relation to change in HbA1c...
August 26, 2016: Diabetes Research and Clinical Practice
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