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GLP-1 Analogues

Antoni Sicras-Mainar, Ruth Navarro-Artieda, Raúl Morano, Lucía Ruíz
OBJECTIVES: The main objective was to assess resource use and costs of starting treatment with insulin or injectable GLP-1 receptor analogues (GLP-1 RAs) in a Spanish population of patients with type 2 diabetes mellitus. Treatment adherence and persistence were also determined for both treatment groups. PATIENTS AND METHODS: A retrospective, non-interventional, observational study was conducted. Patients aged ≥20 years who started treatment with insulin or GLP-1 RAs in the 2010-2012 period were recruited...
October 13, 2016: Endocrinología y Nutrición: órgano de la Sociedad Española de Endocrinología y Nutrición
Jenq-Lin Yang, Wei-Yu Chen, Yin-Ping Chen, Chao-Ying Kuo, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage...
2016: Theranostics
Herpreet Deol, Leoni Lekkakou, Ananth K Viswanath, Joseph M Pappachan
Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre...
September 30, 2016: Endocrine
Chen Qiu, Yan-Ping Wang, Xiao-Dong Pan, Xiao-Ying Liu, Zhou Chen, Li-Bin Liu
BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's disease. Most recently, GLP-1 analogs have been shown to have a significant neuroprotective role in several neurodegenerative diseases. However, few are known on its potential mechanism. OBJECTIVE: In this study, we report the effect of exendin-4 (Ex-4), a GLP-1 receptor agonist, on amyloid-β(1-42) peptide oligomer-induced apoptosis in a PC12 neuronal cell model. METHODS: MTT, DAPI and Annexin-V/PI assays revealed that the viability of PC12 cells decreased in a dose- and time-dependent manner after exposure to amyloid-β(1-42) oligomers...
2016: American Journal of Translational Research
Cecilie Egholm, Makhala Michell Khammy, Thomas Dalsgaard, Aleksandra Mazur, Katerina Tritsaris, Anker Jon Hansen, Christian Aalkjaer, Steen Dissing
We investigated the acute effects of glucagon-like peptides-1 (GLP-1), GLP-1(1-36) and GLP-1(7-36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal L-cells modulates processes related to PLCγ activation, Src and eNOS signaling, thereby controlling endothelial vessel tone. By using RT-PCR we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells (HRMEC) and rat arteries...
September 16, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Yin Lin, Kasper Krogh-Andersen, Julien Pelletier, Harold Marcotte, Claes-Göran Östenson, Lennart Hammarström
Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by intestinal cells and stimulates insulin secretion from the pancreas in a glucose-dependent manner. Exogenously supplied GLP-1 analogues are used in the treatment of type 2 diabetes. An anti-diabetic effect of Lactobacillus in lowering plasma glucose levels and its use as a vehicle for delivery of protein and antibody fragments has been shown previously. The aim of this study was to employ lactobacilli as a vehicle for in situ production and delivery of GLP-1 analogue to normalize blood glucose level in diabetic GK (Goto-Kakizaki) rats...
2016: PloS One
Azazul Islam Chowdhury, Peter Bergsten
Elevated circulating palmitate levels have been connected with type 2 diabetes mellitus. GLP-1 has favorable effects on beta-cells function. The aim was to identify mechanisms for decreased GSIS after long-term palmitate exposure and restoration by GLP-1 by analyzing changes in G-protein coupled receptor (GPCR) pathway signaling. Insulin secretory response to 20 mM glucose was attenuated after 7 days in islets exposed to palmitate but inclusion of exendin-4 restored secretion. Palmitate treatment altered genes of several GPCR signaling pathways including inflammatory pathways with up-regulated IL-1B, SOCS1 and SOCS2 transcript levels...
August 23, 2016: Molecular and Cellular Endocrinology
Everton Cazzo, José Carlos Pareja, Elinton Adami Chaim, Bruno Geloneze, Maria Rita Lazzarini Barreto, Daniéla Oliveira Magro
BACKGROUND: Changes in satiety regulation are known to play a pivotal role in the weight loss effects of Roux-en-Y gastric bypass (RYGB) and the mechanisms by which these changes occur are not entirely known. There are previous reports of the influence of GLP-1 to cause enhancement of satiation, but in regard to GLP-2, it remains unclear. This study aimed to determine whether there is a correlation between the levels of GLP-1 and GLP-2 and satiety regulation following RYGB. MATERIALS AND METHODS: An exploratory prospective cohort study was made which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months...
August 27, 2016: Obesity Surgery
Morgana Prá, Gabriela Kozuchovski Ferreira, Aline Haas de Mello, Rosiane de Bona Schraiber, Larissa Colonetti Cardoso, Luana da Rosa Souza, Naiana da Rosa, Jucélia Jeremias Fortunato, Gislaine Tezza Rezin
Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 μg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated...
October 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Brian DellaValle, Casper Hempel, Trine Staalsoe, Flemming Fryd Johansen, Jørgen Anders Lindholm Kurtzhals
BACKGROUND: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1 (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction. This study investigates the effect of the GLP-1 analogue, liraglutide against the clinical outcome of experimental cerebral malaria (ECM) and Plasmodium falciparum growth...
2016: Malaria Journal
Anna Sowa-Staszczak, Małgorzata Trofimiuk-Müldner, Agnieszka Stefańska, Monika Tomaszuk, Monika Buziak-Bereza, Aleksandra Gilis-Januszewska, Agata Jabrocka-Hybel, Bogusław Głowa, Maciej Małecki, Tomasz Bednarczuk, Grzegorz Kamiński, Aldona Kowalska, Renata Mikołajczak, Barbara Janota, Alicja Hubalewska-Dydejczyk
INTRODUCTION: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. MATERIALS AND METHODS: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions...
2016: PloS One
Tianru Jin, Jianping Weng
GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed "degradation" products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Tengfei Zhou, Mengqian Zhang, Liang Zhao, Aiqin Li, Xiaomei Qin
Oxidative stress and impaired antioxidant defense are believed to be contributors to the cardiovascular aging process. The transcription factor nuclear factor-E2-related factor 2 (Nrf2) plays a key role in orchestrating cellular antioxidant defenses and maintaining redox homeostasis. Our previous study showed that Exendin-4, a glucagon-like peptide-1 analog, alleviates angiotensin II (ANG II)-induced vascular smooth muscle cell (VSMC) senescence by inhibiting Rac1 activation via cAMP/PKA (Zhao L, Li AQ, Zhou TF, Zhang MQ, Qin XM...
October 1, 2016: American Journal of Physiology. Cell Physiology
Jean-Luc Faillie, Oriana H Yu, Hui Yin, Dominique Hillaire-Buys, Alan Barkun, Laurent Azoulay
Importance: The use of dipeptidyl-peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues-a group of drugs used in the management of type 2 diabetes mellitus-may be associated with an increased risk of bile duct and gallbladder disease. To date, no observational study has assessed this possible association. Objective: To determine whether the use of DPP-4 inhibitors and GLP-1 analogues is associated with an increased risk of incident bile duct and gallbladder disease in patients with type 2 diabetes...
October 1, 2016: JAMA Internal Medicine
Priyadarshika Hettiarachchi, A Rajitha Wickremasinghe, Gary S Frost, Kemal I Deen, Ajith A Pathirana, Kevin G Murphy, SriLal D Jayaratne
OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min...
August 2016: Obesity
Nana Li, Yihe Zhao, Yingying Yue, Liming Chen, Zhi Yao, Wenyan Niu
PURPOSE: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, is an antidiabetic drug. It has been shown to improve endothelial dysfunction, but the mechanism remains somewhat unclear. Leptin can also improve endothelial function. Cardiovascular disease (CVD) is linked to hyperleptinemia, and leptin resistance, how liraglutide influences the effect of leptin on endothelial function, is never reported. We used palmitic acid (PA) to mimic hyperlipidemia in endothelial cells to explore the cardio-protective mechanism of liraglutide and its impact on the role of leptin...
September 9, 2016: Biochemical and Biophysical Research Communications
Z Z Htike, T Yates, E M Brady, D Webb, L J Gray, D Swarbrick, G P McCann, K Khunti, M J Davies
BACKGROUND: The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy...
2016: Cardiovascular Diabetology
Sebastian Steven, Kerstin Jurk, Maximilian Kopp, Swenja Kröller-Schön, Yuliya Mikhed, Kathrin Schwierczek, Siyer Roohani, Fatemeh Kashani, Matthias Oelze, Thomas Klein, Sergey Tokalov, Sven Danckwardt, Susanne Strand, Philip Wenzel, Thomas Münzel, Andreas Daiber
BACKGROUND AND PURPOSE: Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibition and supplementation with glucagon-like peptide-1 (GLP-1) analogues improves endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. EXPERIMENTAL APPROACH: Endotoxaemia was induced in C57BL/6 J mice by single injection of lipopolysaccharide (LPS) (17...
July 19, 2016: British Journal of Pharmacology
Bharati Kochar, Millie D Long, Edward Shelton, Lorraine Young, Francis A Farraye, Vijay Yajnik, Hans Herfarth
BACKGROUND: Teduglutide is a GLP-2 analogue indicated for treatment of adults with short bowel syndrome (SBS). Because of the rarity of SBS, real-world safety or efficacy data are not available in patients with Crohn's disease (CD) and SBS treated with teduglutide. AIM: To evaluate teduglutide's safety and efficacy in CD patients with SBS. METHODS: We conducted a retrospective cohort study at 3 tertiary centers in the United States between 2012 and 2014...
July 18, 2016: Journal of Clinical Gastroenterology
Jaishree Jalewa, Mohit Kumar Sharma, Christian Hölscher
Currently, there is no viable treatment available for Parkinson's disease (PD) that stops or reverses disease progression. Interestingly, studies testing the glucagon-like-peptide-1 (GLP-1) mimetic Exendin-4 have shown neuroprotective/neurorestorative properties in pre-clinical tests and in a pilot clinical study of PD. Incretin analogues were originally developed to treat type 2 diabetes and several are currently on the market. In this study, we tested novel incretin analogues on the dopaminergic SH-SY5Y neuroblastoma cells against a toxic mitochondrial complex I inhibitor, Rotenone...
October 2016: Journal of Neurochemistry
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