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https://www.readbyqxmd.com/read/28918389/glucagon-like-peptide-1-receptor-agonists-for-the-management-of-obesity-and-non-alcoholic-fatty-liver-disease-a-novel-therapeutic-option
#1
REVIEW
Gauri Dhir, Kenneth Cusi
Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma...
September 15, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28916246/pre-clinical-toxicology-considerations-for-vaccine-development
#2
REVIEW
Nabil Al-Humadi
Vaccine development requires pre-clinical toxicology studies, following good laboratory practice (GLP), before first in human (phase I) use. Many factors are critical in the final outcome of any pre-clinical toxicology study. The study design is one of these critical factors and should be carefully planned to avoid any false negative and/or false positive results. Preparation is another most critical factor in a successful study. Major changes in any procedure during the course of study should be avoided by all means...
September 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28914987/diabetes-news
#3
Ann M Carracher, Payal H Marathe, Kelly L Close
More than 31,000 attendeesfrom around the world gathered in Barcelona, Spain for the 2017 European Society of Cardiology conference. In presentinga post-hoc analysis of the Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes(LEADER)(1) trial, Dr Neil Poulter (Imperial College London, UK) showedthat results are still positive, indicating cardioprotection, after adjusting for baseline history of stroke or myocardial infarction (MI), which had no mediating effect on the significant association between Novo Nordisk's (Copenhagen, Denmark) glucagon-like peptide-1 (GLP-1) agonist Victoza (liraglutide) and cardiovascular risk reduction...
September 15, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28912925/incretin-kinetics-before-and-after-miglitol-in-japanese-patients-with-late-dumping-syndrome
#4
Mari Amagai, Hirohisa Tsuchiya, Yukari Chiba, Jun Suzuki, Jo Nagakura, Erina Shigematsu, Tadashi Yamakawa, Yasuo Terauchi
BACKGROUND: In patients with late dumping syndrome following gastrectomy, it has been reported that hypoglycemia occurs due to inhibition of glucagon secretion as a result of excessive insulin production facilitated by an increase in glucagon-like peptide-1 (GLP-1). METHODS: To determine the kinetics of incretins in Japanese patients with late dumping syndrome, an oral glucose tolerance test was carried out before and after miglitol administration, and the kinetics of insulin and incretins were analyzed...
October 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#5
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28911306/management-of-blood-pressure-and-heart-rate-in-patients-with-diabetes-mellitus
#6
Ioanna Gouni-Berthold, Ruth Hanssen, Lisa Ravarani, Heiner K Berthold
BACKGROUND: In patients with diabetes mellitus (DM) there is a clear association between blood pressure (BP) levels and macrovascular and microvascular complications. However, the BP targets that need to be achieved for optimal outcomes remain controversial. METHODS: The purpose of this narrative review is to discuss BP targets and management in patients with DM. The subject of elevated heart rate, which has been associated with mortality in many populations, and which is observed in some patients with DM will also be addressed...
June 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28910546/could-hop-derived-bitter-compounds-improve-glucose-homeostasis-by-stimulating-the-secretion-of-glp-1
#7
Luigi Barrea, Giuseppe Annunziata, Giovanna Muscogiuri, Angela Arnone, Gian Carlo Tenore, Annamaria Colao, Silvia Savastano
Hops (Humulus lupulus L.) is by far the greatest contributors to the bitter property of beer. Over the past years, a large body of evidence demonstrated the presence of taste receptors in different locations of the oral cavity. In addition to the taste buds of the tongue, cells expressing these receptors have been identified in olfactory bulbs, respiratory and gastrointestinal tract. In the gut, the attention was mainly directed to sweet Taste Receptor (T1R) and bitter Taste Receptor (T2R) receptors. In particular, T2R has shown to modulate secretion of different gut hormones, mainly Glucagon-like Peptide 1 (GLP-1), which are involved in the regulation of glucose homeostasis and the control of gut motility, thereby increasing the sense of satiety...
September 14, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28910305/aspirin-increases-metabolism-through-germline-signalling-to-extend-the-lifespan-of-caenorhabditis-elegans
#8
Xiao-Bing Huang, Xiao-Hui Mu, Qin-Li Wan, Xiao-Ming He, Gui-Sheng Wu, Huai-Rong Luo
Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased...
2017: PloS One
https://www.readbyqxmd.com/read/28905106/recombinant-mouse-osteocalcin-secreted-by-lactococcus-lactis-promotes-glucagon-like-peptide-1-induction-in-stc-1-cells
#9
Fu Namai, Suguru Shigemori, Koichi Sudo, Takashi Sato, Yoshinari Yamamoto, Shireen Nigar, Tasuku Ogita, Takeshi Shimosato
An osteoblastic protein, osteocalcin (OC), exists in vivo in two forms: carboxylated OC, and uncarboxylated or low-carboxylated OC (ucOC). ucOC acts as a hormone to regulate carbon and energy metabolism. Recent studies demonstrated that ucOC exerts insulinotropic effects, mainly through the glucagon-like peptide 1 (GLP-1) pathway. GLP-1 is an insulinotropic hormone secreted by enteroendocrine L cells in the small intestine. Thus, efficient delivery of ucOC to the small intestine may be a new therapeutic option for metabolic diseases such as diabetes and obesity...
September 13, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28903493/editor-s-highlight-formulation-and-toxicology-evaluation-of-the-intrathecal-ayx1-dna-decoy-in-sprague-dawley-rats
#10
Julien Mamet, David C Yeomans, Tony L Yaksh, Donald C Manning, Scott Harris
The longevity of pain after surgery is debilitating and limits the recovery of patients. AYX1 is a double-stranded, unprotected, 23 base-pair oligonucleotide designed to reduce acute post-surgical pain and prevent its chronification with a single intrathecal perioperative dose. AYX1 mimics the DNA sequence normally bound by EGR1 on chromosomes, a transcription factor transiently induced in the dorsal root ganglia-spinal cord network following a noxious input. AYX1 binds to EGR1 and prevents it from launching waves of gene regulation that are necessary to maintain pain over time...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903385/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#11
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4(D)) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4(D)) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4(D), (3) KIR-F344 (4) KIR-DPP4(D), (5) DPP4(D)-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4(D) rats 72 h after acute KIR...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898910/balanced-coagonist-of-glp-1-and-glucagon-receptors-corrects-dyslipidemia-by-improving-fgf21-sensitivity-in-hamster-model
#12
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Hiren M Patel, Dheerendra Pandey, Dipam Patel, Brijesh Sutariya, Maulik Patel, Rajesh Bahekar, Mukul R Jain
Hyperlipidemia is often associated with obesity and diabetes, and can lead to serious complications like atherosclerosis and fatty liver disease. Coagonist of GLP-1 and glucagon receptors is a therapy under clinical investigation for treatment of obesity and diabetes. In this study, we have characterized the mechanism of hypolipidemic effect of a balanced coagonist using high cholesterol-fed hamsters. Tyloxapol-induced hypertriglyceridemia, lipolysis in adipose tissue, and bile homeostasis were assessed after repeated dose treatment of the coagonist of GLP-1 and glucagon receptors (Aib2 C24 chimera 2, SC)...
September 12, 2017: Drug Research
https://www.readbyqxmd.com/read/28895639/the-pi3k-akt1-foxo1-translocation-pathway-mediates-exf-effects-on-nit-1-cell-survival
#13
Guo-Jiang Hou, Cai-Na Li, Yi Huan, Shuai-Nan Liu, Quan Liu, Min-Zhi Liu, Zhu-Fang Shen
EXf, a glucagon-like peptide 1 (GLP-1) receptor agonist, stimulates β-cell proliferation and reduces apoptosis in diabetic animal models, but the underlying mechanisms are not fully understood. We constructed a FoxO1-GFP fusion protein expression plasmid and transiently transfected it into NIT-1 cells to investigate whether FoxO1 mediates EXf effects on NIT-1 cell survival. Our results showed that EXf could increase cell viability by inhibiting apoptosis and stimulating proliferation, and it could also promote the translocation of the FoxO1-GFP fusion protein from the nucleus to the cytoplasm in NIT-1 cells...
September 11, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#14
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894993/effect-of-growth-hormone-overexpression-on-gastric-evacuation-rate-in-coho-salmon
#15
Jin-Hyoung Kim, Satid Chatchaiphan, Michelle T Crown, Samantha L White, Robert H Devlin
Growth hormone (GH) transgenic (T) coho salmon consistently show remarkably enhanced growth associated with increased appetite and food consumption compared to non-transgenic wild-type (NT) coho salmon. To improve understanding of the mechanism by which GH overexpression mediates food intake and digestion in T fish, feed intake and gastric evacuation rate (over 7 days) were measured in size-matched T and NT coho salmon. T fish displayed greatly enhanced feed intake levels (~ 2.5-fold), and more than 3-fold increase in gastric evacuation rates relative to NT coho salmon...
September 11, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#16
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#17
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28893239/association-of-tcm-body-constitution-with-insulin-resistance-and-risk-of-diabetes-in-impaired-glucose-regulation-patients
#18
Hong You, Tong Zhang, Wen Feng, Yun Gai
BACKGROUND: Impaired glucose regulation (IGR) patients have increased risk of type 2 diabetes mellitus (T2DM). Identifying relevant risk factors in IGR subjects could facilitate early detection and prevention of IGR progression to diabetes. This study investigated the association between Traditional Chinese Medicine (TCM) body constitution and serum cytokines, and whether body constitution could independently predict diabetes in IGR subjects. METHOD: Patients with IGR (n = 306) received a blood test and their body constitution type was assessed using a body constitution questionnaire (BCQ)...
September 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28892258/sitagliptin-and-roux-en-y-gastric-bypass-modulate-insulin-secretion-via-regulation-of-intra-islet-pyy
#19
Claudia Guida, Laura J McCulloch, Mahdieh Godazgar, Sam D Stephen, Charlotte Baker, Davide Basco, Jiawen Dong, Duan Chen, Anne Clark, Reshma D Ramracheya
AIMS: The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme DPP-IV has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS)...
September 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28891030/species-differences-in-pancreatic-binding-of-do3a-vs-cys-40-exendin4
#20
Olof Eriksson, Ulrika Rosenström, Ram K Selvaraju, Barbro Eriksson, Irina Velikyan
AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed. METHODS: In vitro and ex vivo autoradiography studies of pancreas were performed using [(177)Lu]Lu-DO3A-VS-Cys(40)-Exendin4, in order to investigate the mechanism of uptake as well as the islet uptake contrast in mouse, rat, pig, and non-human primate...
September 11, 2017: Acta Diabetologica
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