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https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#1
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28443255/glucagon-like-peptide-1-and-glucagon-like-peptide-1-receptor-agonists-in-the-treatment-of-type-2-diabetes
#2
REVIEW
Seungah Lee, Dong Yun Lee
The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic β-cell insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide...
March 2017: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#3
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28435305/glucagon-like-peptide-1-receptor-agonists-a-systematic-review-of-comparative-effectiveness-research
#4
REVIEW
Philip A Levin, Hiep Nguyen, Eric T Wittbrodt, Seoyoung C Kim
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. OBJECTIVE: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. METHODS: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28435304/comparative-effectiveness-of-glycemic-control-in-patients-with-type-2-diabetes-treated-with-glp-1-receptor-agonists-a-network-meta-analysis-of-placebo-controlled-and-active-comparator-trials
#5
Michelle E Orme, Hiep Nguyen, Jackie Y Lu, Susan A Thomas
BACKGROUND: Clinical studies of patients with type 2 diabetes show that GLP-1 receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss. We conducted a Bayesian network meta-analysis (NMA) of placebo- and active-controlled randomized trials to assess the comparative effectiveness of liraglutide, albiglutide, dulaglutide, and exenatide twice daily and once weekly, with a focus on glycemic control. MATERIALS AND METHODS: We searched Medline, Embase, and the Cochrane Library (up to December 2014) for core registration programs for US-approved GLP-1 RAs...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#6
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28376799/new-association-of-bone-morphogenetic-protein-4-concentrations-with-fat-distribution-in-obesity-and-exenatide-intervention-on-it
#7
Xingchun Wang, Jiaqi Chen, Liang Li, Cui Ling Zhu, Jingyang Gao, Sharvan Rampersad, Le Bu, Shen Qu
BACKGROUND: Bone morphogenetic protein 4 (BMP-4) has been proven to regulate white adipogensis. We aimed to demonstrate the correlation of BMP-4 with fat distribution and Exenatide treatment on it. METHODS: We enrolled 69 obese patients. Anthropometric and metabolic indexes were collected. Fat distribution was measured by dual-energy X-ray absorptiometry. BPM-4 levels were assessed using enzyme-link immunosorbent assay kit. 30 obese patients were treated with Exenatide twice a day...
April 4, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28368384/glp-1-acts-on-habenular-avoidance-circuits-to-control-nicotine-intake
#8
Luis M Tuesta, Zuxin Chen, Alexander Duncan, Christie D Fowler, Masago Ishikawa, Brian R Lee, Xin-An Liu, Qun Lu, Michael Cameron, Matthew R Hayes, Theodore M Kamenecka, Matthew Pletcher, Paul J Kenny
Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28345814/dapagliflozin-once-daily-plus-exenatide-once-weekly-in-obese-adults-without-diabetes-sustained-reductions-in-bodyweight-glycaemia-and-blood-pressure-over-1-year
#9
Per Lundkvist, Maria J Pereira, Petros Katsogiannos, C David Sjöström, Eva Johnsson, Jan W Eriksson
AIMS: Dapagliflozin and exenatide reduce bodyweight by differing mechanisms. Dual therapy with these agents reduces bodyweight, adipose tissue volume, glycaemia, and systolic blood pressure (SBP) over 24 weeks. Here, we examined these effects over 1 year in obese adults without diabetes. MATERIALS AND METHODS: Obese adults without diabetes (N = 50; aged 18-70 years; body mass index 30-45 kg/m(2) ) initially randomized to double-blind oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo entered an open-label extension from 24-52 weeks during which all participants received active treatment...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#10
REVIEW
Hamish Courtney, Rahul Nayar, Chinnadorai Rajeswaran, Ravi Jandhyala
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#11
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#12
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, considerable disagreement exists on whether incretins actually increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
March 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#13
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28315192/discrete-choice-experiment-attribute-selection-using-a-multinational-interview-study-treatment-features-important-to-patients-with-type-2-diabetes-mellitus
#14
Anna Rydén, Stephanie Chen, Emuella Flood, Beverly Romero, Susan Grandy
INTRODUCTION: Methods for discrete choice experiment (DCE) attribute and attribute-level selection have not yet been firmly established and are rarely reported in detail. This paper describes a qualitative study designed to inform the development of a DCE survey designed to examine preferences for glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments among patients with type 2 diabetes mellitus. METHODS: The study involved a literature review, interviews with clinical experts, and interviews with GLP-1RA-experienced (i...
March 17, 2017: Patient
https://www.readbyqxmd.com/read/28283565/assessment-of-pancreas-safety-in-the-development-program-of-once-weekly-glp-1-receptor-agonist-dulaglutide
#15
Michael A Nauck, Jean-Louis Frossard, Jamie S Barkin, Greg Anglin, Ingrid E Hensley, Kristine D Harper, Zvonko Milicevic
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks...
March 10, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#16
Dominic-Luc Webb, Niclas Abrahamsson, Magnus Sundbom, Per M Hellström
Obesity with a body mass index (BMI) over 30 kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass...
June 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#17
REVIEW
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28274877/exenatide-improves-liver-mitochondrial-dysfunction-and-insulin-resistance-by-reducing-oxidative-stress-in-high-fat-diet-induced-obese-mice
#18
Zixuan Wang, Lin Hou, Lanhui Huang, Jun Guo, Xinli Zhou
Oxidative stress is associated with obesity and may be accompanied by liver insulin resistance and mitochondrial dysfunction. Decreased mitochondrial respiratory chain enzymatic activities and decreased insulin metabolic signaling may promote these maladaptive changes. In this context, exenatide has been reported to reduce hepatic lipid deposition, improve insulin sensitivity and improve mitochondrial dysfunction. We hypothesized that exenatide would attenuate mitochondrial dysfunction by reducing hepatic lipid deposition, blunting oxidant stress and promoting insulin metabolic signaling in a high fat diet-induced model of obesity and insulin resistance...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28260235/no-cognitive-enhancing-effect-of-glp-1-receptor-agonism-in-antipsychotic-treated-obese-patients-with-schizophrenia
#19
P L Ishøy, B Fagerlund, B V Broberg, N Bak, F K Knop, B Y Glenthøj, B H Ebdrup
OBJECTIVE: Schizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive-enhancing effects. In this investigator-initiated, double-blind, randomized, placebo-controlled trial, we tested non-metabolic effects of exenatide once-weekly (Bydureon™) in obese, antipsychotic-treated patients with schizohrenia spectrum disorder. METHOD: Before and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey-Osterreith complex figure test (REY), Short-Form Health Survey (SF-36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS)...
March 5, 2017: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#20
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
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