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https://www.readbyqxmd.com/read/28645107/effects-of-liraglutide-on-hemodynamic-parameters-in-patients-with-heart-failure
#1
Jin Ying Zhang, Xin Yun Wang, Xiang Wang
Glucagon-like peptide-1 analogues improve left ventricular function in patients with acute myocardial infarction. This study aimed to evaluate the effects of liraglutide on hemodynamic parameters in patients with heart failure. A total of 78 patients with heart failure were enrolled in this study between August 2014 and November 2015. Of these, 52 patients were randomized 1:1 to receive either liraglutide or placebo for 7 days. Hemodynamic measurements were made using transpulmonary thermodilution and arterial pulse contour analysis...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643938/oral-application-of-a-periodontal-pathogen-impacts-serpine1-expression-and-pancreatic-islet-architecture-in-prediabetes
#2
V Ilievski, U G Bhat, S Suleiman-Ata, B A Bauer, P T Toth, S T Olson, T G Unterman, K Watanabe
BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 β cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28642113/paralog-divergent-features-may-help-reduce-off-target-effects-of-drugs-hints-from-glucagon-subfamily-analysis
#3
Zhining Sa, Jingqi Zhou, Yangyun Zou, Zhixi Su, Xun Gu
Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes...
June 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#4
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#5
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28637886/cardiovascular-disease-and-type-2-diabetes-has-the-dawn-of-a-new-era-arrived
#6
Muhammad Abdul-Ghani, Ralph A DeFronzo, Stefano Del Prato, Robert Chilton, Rajvir Singh, Robert E J Ryder
Hyperglycemia is the major risk factor for microvascular complications in patients with type 2 diabetes (T2D). However, cardiovascular disease (CVD) is the principal cause of death, and lowering HbA1c has only a modest effect on reducing CVD risk and mortality. The recently published LEADER and SUSTAIN-6 trials demonstrate that, in T2D patients with high CVD risk, the glucagon-like peptide 1 receptor agonists liraglutide and semaglutide reduce the primary major adverse cardiac events (MACE) end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) by 13% and 24%, respectively...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28637406/socioeconomic-status-the-missing-link-between-obesity-and-diabetes-mellitus
#7
Alexei Volaco, Ana Maria Cavalcanti, Roberto Pecoits Filho, Dalton Bertolim Précoma
BACKGROUND: Currently, there is an epidemic expansion of the obesity rates worldwide. The increasing number of obese individuals associated with the aging of population leads to increasing number of individuals with type 2 diabetes mellitus (T2DM) at the same rate. The traditional factors that link obesity to T2DM are related to genetics, hypercaloric diet, sedentary lifestyle, and stress. Individuals from lower socioeconomic status (SES) have restricted autonomy and opportunities that could lead to more stress and consequently increase in stress hormones, such as cortisol, catecholamines, glucagon, and growth hormone, which might ultimately change fat deposition, increasing visceral fat and increasing the risk of T2DM mellitus development...
June 21, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28636871/pregnane-glycosides-from-cynanchum-menarandrense
#8
Michail Tsoukalas, Arianna Psichas, Frank Reimann, Fiona M Gribble, Annelise Lobstein, Aurélie Urbain
Five new pregnane-type steroidal glycosides, named menarandrosides A-E (1-2, 5-7) were isolated from the aerial parts of Cynanchum menarandrense, together with three known compounds, carumbelloside I (3), carumbelloside II (4), and pregnenolone-3-O-gentiobioside (8). Their structures were determined on the basis of spectroscopic analyses including NMR and mass spectrometry, reporting C-21 steroids glycosylated only by one or two glucose moieties. Compounds were then investigated for their potential to stimulate glucagon-like peptide-1 (GLP-1) secretion in intestinal cells; although none of the pure compounds had any influence, the fraction enriched in pregnanes exhibited a significant activity, suggesting a possible synergistic effect...
June 18, 2017: Steroids
https://www.readbyqxmd.com/read/28635330/multiple-functions-of-insulin-degrading-enzyme-a-metabolic-crosslight
#9
Grazia R Tundo, Diego Sbardella, Chiara Ciaccio, Giuseppe Grasso, Magda Gioia, Andrea Coletta, Fabio Polticelli, Donato Di Pierro, Danilo Milardi, Peter Van Endert, Stefano Marini, Massimo Coletta
Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as β-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#10
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634585/high-plasma-glucagon-levels-correlate-with-waist-to-hip-ratio-suprailiac-skinfold-thickness-and-deep-subcutaneous-abdominal-and-intraperitoneal-adipose-tissue-depots-in-nonobese-asian-indian-males-with-type-2-diabetes-in-north-india
#11
Shajith Anoop, Anoop Misra, Surya Prakash Bhatt, Seema Gulati, Harsh Mahajan, Gokulraj Prabakaran
We aimed to correlate plasma glucagon levels with anthropometric measures and abdominal adipose tissue depots. Nonobese males (n = 81; BMI < 25 kg/m(2)) with T2DM of less than one-year duration and nonobese males without diabetes (n = 30) were evaluated for the following: anthropometry (BMI, waist circumference, W-HR, and truncal skinfolds), whole-body DEXA (for body fat and fat-free mass), and MRI scan (for volumes of subcutaneous abdominal adipose tissue (SCAT) including superficial and deep, intra-abdominal visceral adipose tissue (including intraperitoneal adipose tissue (IPAT), retroperitoneal adipose tissue, liver span and fatty liver, and pancreatic volume))...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28633506/role-of-glucagon-like-peptide-1and-gastric-inhibitory-peptide-in-anorexia-induction-following-oral-exposure-to-the-trichothecene-mycotoxin-deoxynivalenol-vomitoxin
#12
Hui Jia, Wen-Da Wu, Xi Lu, Jie Zhang, Cheng-Hua He, Hai-Bin Zhang
Deoxynivalenol (DON), which is a Type B trichothecene mycotoxin produced by Fusarium, frequently contaminates cereal staples, such as wheat, barley and corn. DON threatens animal and human health by suppressing food intake and impairing growth. While anorexia induction in mice exposed to DON has been linked to the elevation of the satiety hormones cholecystokinin (CCK) and peptide YY3-36(PYY3-36) in plasma, the effects of DON on the release of other satiety hormones, such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), have not been established...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28632997/epidemiology-of-obesity-and-pharmacologic-treatment-options
#13
Vignesh Shettar, Sarang Patel, Srividya Kidambi
Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety...
June 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28631762/-safety-and-tolerability-of-oral-hypoglycemic-therapies-in-type-2-diabetes-mellitus-patients-at-high-cardiovascular-risk
#14
Giuseppe Ambrosio, Gaetano M De Ferrari, Massimo Federici, Pasquale Perrone Filardi
Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia...
June 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28630704/the-effects-of-a-post-exercise-carbohydrate-and-protein-supplement-on-repeat-performance-serum-chemistry-insulin-and-glucagon-in-competitive-weight-pulling-dogs
#15
Christopher W Frye, Gretchen M VanDeventer, Gina K Dinallo, Jennifer A Poplarski, Sabine Mann, Ella Pittman, Brian M Zanghi, Joseph J Wakshlag
The physiological demands of weight-pulling dogs have yet to be investigated. Two groups of competitive weight-pulling dogs both underwent two identical pull series 3 h apart. The control group (n 8) was compared with a group fed a rapidly digestible carbohydrate and protein supplement after the first pull series (n 9). Blood was drawn before and after each pull series as well as at 15 and 30 min after the first pull series finished. Biochemistry values remained unremarkable throughout the study in both groups regardless of supplementation or exercise over time...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#16
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28630069/degradation-of-incretins-and-modulation-of-blood-glucose-levels-by-periodontopathic-bacterial-dipeptidyl-peptidase-4
#17
Yuko Ohara-Nemoto, Manami Nakasato, Yu Shimoyama, Tomomi T Baba, Takeshi Kobayakawa, Toshio Ono, Takashi Yaegashi, Shigenobu Kimura, Takayuki K Nemoto
Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28629388/the-albumin-exendin-4-recombinant-protein-e2hsa-improves-glycemic-control-and-%C3%AE-cell-function-in-spontaneous-diabetic-kkay-mice
#18
Caina Li, Shaocong Hou, Shuainan Liu, Yi Huan, Sujuan Sun, Quan Liu, Zhufang Shen
BACKGROUND: E2HSA is a genetic fusion protein that consists of two tandem exendin-4 molecules that are covalently bonded to recombinant human serum albumin via a peptide linker. Previous studies have demonstrated that E2HSA significantly decreased blood glucose levels, improved β-cell function and promoted β-cell proliferation in diabetic db/dB mice. This study aimed to evaluate the benefits of E2HSA on glucose and lipid metabolism in a spontaneous diabetes animal model, KKAy mice. METHODS: E2HSA was acutely administered at doses of 1, 3 and 9 mg/kg by subcutaneous injection in diabetic KKAy mice with exendin-4 (2 μg/kg) as a positive reference, and then the non-fasting blood glucose and food intake levels were dynamically monitored...
June 19, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28627773/oleanolic-acid-derivative-dks26-exerts-antidiabetic-and-hepatoprotective-effects-in-diabetic-mice-and-promotes-glp-1-secretion-and-expression-in-intestinal-cells
#19
Fei-Fei Chen, Jian-Ta Wang, Li-Xia Zhang, Shu-Fang Xing, Yun-Xia Wang, Kai Wang, Shu-Li Deng, Ji-Quan Zhang, Lei Tang, Hao-Shu Wu
BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP-1 related antidiabetic mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: The therapeutic effects of DKS26 were inspected in streptozotocin (STZ)-induced and db/db diabetic mouse models including levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro-inflammation cytokines...
June 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28627654/bioinformatics-analysis-of-transcription-profiling-of-solid-pseudopapillary-neoplasm-of-the-pancreas
#20
Yongping Zhang, Xu Han, Hao Wu, Yifeng Zhou
Solid pseudopapillary neoplasm (SPN) of the pancreas is a low-grade malignant neoplasm that accounts for ~5% of cystic pancreatic tumors and ~0.9‑2.7% of exocrine pancreatic tumors. The transcription profiling data (GSE43795) of 14 SPN and 6 control samples were downloaded from the Gene Expression Omnibus (GEO) database. Using the Limma package, Student's t‑tests were performed to identify differentially expressed genes (DEGs) between SPN and control samples [with the following criterion: False discovery rate (FDR)<0...
June 19, 2017: Molecular Medicine Reports
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