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Diabetes, obesity, glp-1,heart

Yanna Lei, Lina Hu, Guang Yang, Limei Piao, Minggen Jin, Xianwu Cheng
Dipeptidyl peptidase IV (DPP-IV) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase and transmits intracellular signals through a small intracellular tail. DPP-IV exists in human blood in a soluble form, and truncates a large number of peptide hormones, chemokines, cytokines, and growth factors in vitro and in vivo. DPP-IV has gained considerable interest as a therapeutic target, and a variety of DPP-IV inhibitors that prolong the insulinotropic effects of glucagon-like peptide-1 (GLP-1) are widely used in clinical settings as antidiabetic drugs...
March 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
Kendra R Manigault, Maria Miller Thurston
OBJECTIVE: To review the efficacy and safety of liraglutide 3.0 mg for weight loss. DATA SOURCE: A literature search was performed using PubMed and MEDLINE from 2000 to 2016. The following key terms were used alone or in combination: glucagon-like peptide-1 agonist, liraglutide, obesity, overweight, and weight loss. Additional supporting literature was identified utilizing the reference lists of the preceding articles. STUDY SELECTION: Analyzed studies were published in English and investigated use of liraglutide and its impact on weight loss...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and glucose-dependent insulinotropic polypeptide, exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor agonists and dipeptidyl peptidase-4 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...
December 2016: Endocrine Reviews
Eun Ju Bae
Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are an emerging class of antidiabetic drugs that constitutes approximately fifty percent of the market share of the oral hypoglycemic drugs. Its mechanism of action for lowering blood glucose is essentially via inhibition of the rapid degradation of incretin hormones, such as glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide (GIP), thus the plasma concentration of GLP-1 increases, which promotes insulin secretion from the pancreatic β cells and suppresses glucagon secretion from the α cells...
August 2016: Archives of Pharmacal Research
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...
July 21, 2016: Cardiovascular Diabetology
Sharon P G Fowler
For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators' work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs - including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol+aspartame - have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or - in many cases - even to calorically-sweetened foods or liquids...
October 1, 2016: Physiology & Behavior
Julie A Lovshin, Annette Barnie, Ariana DeAlmeida, Alexander Logan, Bernard Zinman, Daniel J Drucker
OBJECTIVE: GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR). RESEARCH DESIGN AND METHODS: Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting...
January 2015: Diabetes Care
Mitchel Tate, Aaron Chong, Emma Robinson, Brian D Green, David J Grieve
Glucagon-like peptide-1 (GLP-1) is an incretin hormone whose glucose-dependent insulinotropic actions have been harnessed as a novel therapy for glycaemic control in type 2 diabetes. Although it has been known for some time that the GLP-1 receptor is expressed in the CVS where it mediates important physiological actions, it is only recently that specific cardiovascular effects of GLP-1 in the setting of diabetes have been described. GLP-1 confers indirect benefits in cardiovascular disease (CVD) under both normal and hyperglycaemic conditions via reducing established risk factors, such as hypertension, dyslipidaemia and obesity, which are markedly increased in diabetes...
February 2015: British Journal of Pharmacology
G Muscogiuri, A Cignarelli, F Giorgino, F Prodam, F Prodram, D Santi, G Tirabassi, G Balercia, R Modica, A Faggiano, A Colao
INTRODUCTION: Glucagon-like peptide 1 (GLP-1) is an intestinal hormone secreted after the ingestion of various nutrients. The main role of GLP-1 is to stimulate insulin secretion in a glucose-dependent manner. However, the expression of GLP-1 receptor was found to be expressed in a variety of tissues beyond pancreas such as lung, stomach, intestine, kidney, heart and brain. Beyond pancreas, a beneficial effect of GLP-1 on body weight reduction has been shown, suggesting its role for the treatment of obesity...
December 2014: Journal of Endocrinological Investigation
Annayya R Aroor, James R Sowers, Guanghong Jia, Vincent G DeMarco
Dipeptidylpeptidase-4 (DPP-4) is a ubiquitously expressed transmembrane protein that removes NH2-terminal dipeptides from various substrate hormones, chemokines, neuropeptides, and growth factors. Two known substrates of DPP-4 include the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide, which are secreted by enteroendocrine cells in response to postprandial hyperglycemia and account for 60–70% of postprandial insulin secretion. DPP-4 inhibitors (DPP-4i) block degradation of GLP-1 and gastric inhibitory peptide, extend their insulinotropic effect, and improve glycemia...
August 15, 2014: American Journal of Physiology. Heart and Circulatory Physiology
Adam G Goodwill, Kieren J Mather, Abass M Conteh, Daniel J Sassoon, Jillian N Noblet, Johnathan D Tune
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has been shown to have hemodynamic and cardioprotective capacity in addition to its better characterized glucoregulatory actions. Because of this, emerging research has focused on the ability of GLP-1 based therapies to drive myocardial substrate selection, enhance cardiac performance and regulate heart rate, blood pressure and vascular tone. These studies have produced consistent and reproducible results amongst numerous laboratories. However, there are obvious disparities in findings obtained in small animal models versus those of higher mammals...
September 2014: Reviews in Endocrine & Metabolic Disorders
Simon Comerma-Steffensen, Martin Grann, Charlotte U Andersen, Jorgen Rungby, Ulf Simonsen
The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity...
May 2014: Current Vascular Pharmacology
Yutaka Seino, Daisuke Yabe
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine on ingestion of various nutrients to stimulate insulin secretion from pancreatic β-cells glucose-dependently. GIP and GLP-1 undergo degradation by dipeptidyl peptidase-4 (DPP-4), and rapidly lose their biological activities. The actions of GIP and GLP-1 are mediated by their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are expressed in pancreatic β-cells, as well as in various tissues and organs...
March 18, 2013: Journal of Diabetes Investigation
Zemin Yao
No abstract text is available yet for this article.
2014: Cardiovascular & Hematological Disorders Drug Targets
J Seufert, B Gallwitz
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta-cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP-1 receptors are also expressed in extra-pancreatic tissues and trial data suggest that GLP-1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP-1 or GLP-1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes...
August 2014: Diabetes, Obesity & Metabolism
T S Han, F C W Wu, M E J Lean
The rising rate of overweight/obesity among the ever-growing ageing population is imposing massive and rapidly changing burdens of ill health. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults, mainly through its reduced impact on coronary heart disease, has often been misinterpreted that obesity is not as harmful in the elderly, who suffer a large range of disabling consequences of obesity. All medical consequences of obesity are multi-factorial and most alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy...
August 2013: Best Practice & Research. Clinical Endocrinology & Metabolism
Steven P Moberly, Kieren J Mather, Zachary C Berwick, Meredith K Owen, Adam G Goodwill, Eli D Casalini, Gary D Hutchins, Mark A Green, Yen Ng, Robert V Considine, Kevin M Perry, Robin L Chisholm, Johnathan D Tune
Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM...
July 2013: Basic Research in Cardiology
Akio Monji, Toko Mitsui, Yasuko K Bando, Morihiko Aoyama, Toshimasa Shigeta, Toyoaki Murohara
Glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) is a remedy for type 2 diabetes mellitus (T2DM). Ex-4 ameliorates cardiac dysfunction induced by myocardial infarction in preclinical and clinical settings. However, it remains unclear whether Ex-4 may modulate diabetic cardiomyopathy. We tested the impact of Ex-4 on two types of diabetic cardiomyopathy models, genetic (KK) and acquired T2DM induced by high-fat diet [diet-induced obesity (DIO)], to clarify whether Ex-4 may combat independently of etiology...
August 1, 2013: American Journal of Physiology. Heart and Circulatory Physiology
P Valensi, S Chiheb, M Fysekidis
Heart rate (HR) predicts cardiovascular morbidity and mortality in individuals either with or without diabetes. In type 2 diabetic patients, cardiac autonomic neuropathy is a risk marker for cardiac morbidity and mortality. A major pathogenic potential may be attributed to vagal depression and sympathetic predominance. In this issue of Diabetologia, Berkelaar et al (DOI: 10.1007/s00125-013-2848-6 ) examined the effects of euglycaemic, and hyperglycaemic clamp with the addition of glucagon-like-peptide-1 (GLP-1) and arginine, on cardiac vagal control in a large number of healthy subjects...
June 2013: Diabetologia
Miguel Camafort-Babkowski
Anti-diabetic drugs have, in addition to their well-known glucose lowering-effect, different effects in the rest of cardiovascular factors that are associated with diabetes mellitus. Glucagon-like peptide-1 (GLP-1) receptor agonists have recently been incorporated to the therapeutic arsenal of type 2 diabetes mellitus. The objective of this review is to summarize the available evidence on the effect of the GLP-1 receptor agonists on different cardiovascular risk factors, mediated by the effect of GLP-1 receptor agonists on the control of hyperglycaemia and the GLP-1 receptor agonists effect on other cardiovascular risk factors (weight control, blood pressure control, lipid profile and all other cardiovascular risk biomarkers)...
August 17, 2013: Medicina Clínica
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