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GLP-1 diabetes obesity

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https://www.readbyqxmd.com/read/30513818/thromboxane-dependent-platelet-activation-in-obese-subjects-with-prediabetes-or-early-type-2-diabetes-effects-of-liraglutide-or-lifestyle-changes-induced-weight-loss
#1
Paola Simeone, Rossella Liani, Romina Tripaldi, Augusto Di Castelnuovo, Maria Teresa Guagnano, Armando Tartaro, Riccardo C Bonadonna, Virginia Federico, Francesco Cipollone, Agostino Consoli, Francesca Santilli
Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXB₂ and 8-iso-prostaglandin (PG)F2α , play a key role in atherothrombosis in obesity and type 2 diabetes mellitus (T2DM) since the earlier stages. Thirty-five metformin-treated obese subjects with prediabetes or newly-diagnosed T2DM were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/day) or lifestyle counseling until achieving a comparable weight loss (-7% of initial body weight), to assess whether changes in subcutaneous (SAT) and visceral (VAT) adipose tissue distribution (MRI), insulin sensitivity (Matsuda Index) and beta-cell performance (multiple sampling OGTT beta-index), with either intervention, might affect TX-dependent platelet activation, lipid peroxidation and inflammation...
December 2, 2018: Nutrients
https://www.readbyqxmd.com/read/30499633/exendin-4-lys-27-pal-gastrin-xenin-8-gln-a-novel-acylated-glp-1-gastrin-xenin-hybrid-peptide-that-improves-metabolic-status-in-obese-diabetic-ob-ob-mice
#2
Annie Hasib, Ming T Ng, Neil Tanday, Sarah L Craig, Victor A Gault, Peter R Flatt, Nigel Irwin
BACKGROUND: Therapeutic benefits of peptide-based drugs is limited by rapid renal elimination. METHODS: Therefore, to prolong the biological action profile of the recently characterised triple-acting hybrid peptide, exendin-4/gastrin/xenin-8-Gln, a fatty-acid (C-16) has been covalently attached, creating exendin-4(Lys27 PAL)/gastrin/xenin-8-Gln. Exendin-4/gastrin and liraglutide/gastrin/xenin-8-Gln were also synthesised as direct comparator peptides. RESULTS: All hybrid peptides evoked significant concentration-dependent increases of insulin secretion from isolated murine islets and BRIN-BD11 cells...
November 30, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/30487448/chronic-exposure-to-palmitate-impairs-insulin-signaling-in-an-intestinal-l-cell-line-a-possible-shift-from-glp-1-to-glucagon-production
#3
Agnese Filippello, Francesca Urbano, Stefania Di Mauro, Alessandra Scamporrino, Antonino Di Pino, Roberto Scicali, Agata Maria Rabuazzo, Francesco Purrello, Salvatore Piro
Obesity and type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and impaired glucagon-like peptide-1 (GLP-1) secretion/function. Lipotoxicity, a chronic elevation of free fatty acids in the blood, could affect insulin-signaling in many peripheral tissues. To date, the effects of lipotoxicity on the insulin receptor and insulin resistance in the intestinal L-cells need to be elucidated. Moreover, recent observations indicate that L-cells may be able to process not only GLP-1 but also glucagon from proglucagon...
November 28, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30473097/ly3298176-a-novel-dual-gip-and-glp-1-receptor-agonist-for-the-treatment-of-type-2-diabetes-mellitus-from-discovery-to-clinical-proof-of-concept
#4
Tamer Coskun, Kyle W Sloop, Corina Loghin, Jorge Alsina-Fernandez, Shweta Urva, Krister B Bokvist, Xuewei Cui, Daniel A Briere, Over Cabrera, William C Roell, Uma Kuchibhotla, Julie S Moyers, Charles T Benson, Ruth E Gimeno, David A D'Alessio, Axel Haupt
OBJECTIVE: A novel dual GIP and GLP-1 receptor agonist, LY3298176, was developed to determine whether the metabolic action of GIP adds to the established clinical benefits of selective GLP-1 receptor agonists in type 2 diabetes mellitus (T2DM). METHODS: LY3298176 is a fatty acid modified peptide with dual GIP and GLP-1 receptor agonist activity designed for once-weekly subcutaneous administration. LY3298176 was characterised in vitro, using signaling and functional assays in cell lines expressing recombinant or endogenous incretin receptors, and in vivo using body weight, food intake, insulin secretion and glycemic profiles in mice...
December 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/30466162/cracking-the-combination-gut-hormones-for-the-treatment-of-obesity-and-diabetes
#5
REVIEW
Kleopatra Alexiadou, Olawaseun Anyiam, Tricia Tan
Obesity and type 2 diabetes are a veritable global pandemic. There is an imperative to develop new therapies for these conditions that can be delivered at scale to patients, which deliver effective and titratable weight loss, amelioration of diabetes, prevention of diabetic complications and improvements in cardiovascular health. Although agents based on glucagon-like peptide-1 (GLP-1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required. By combining the effects of GLP-1 with other gut and metabolic hormones such as glucagon (GCG), oxyntomodulin, glucose-dependent insulinotropic peptide (GIP) and peptide YY, we may obtain improved weight loss, increased energy expenditure and improved metabolic profiles...
November 22, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/30465123/body-weight-considerations-in-the-management-of-type-2-diabetes
#6
REVIEW
Caroline M Apovian, Jennifer Okemah, Patrick M O'Neil
Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis. Modest weight-loss (≥ 5% but < 10%) can minimize and reduce diabetes-associated complications, and significant weight-loss can potentially resolve disease. Treatment guidelines recommend that intensive lifestyle interventions, pharmacologic therapy, and/or metabolic surgery be considered as options for patients with T2D and obesity. The benefits and risks of such interventions should be evaluated in the context of their weight-loss potential, ability to sustain weight change, side effect profile, and costs...
November 21, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/30459715/future-perspectives-on-glp-1-receptor-agonists-and-glp-1-glucagon-receptor-co-agonists-in-the-treatment-of-nafld
#7
REVIEW
Marta Seghieri, Alexander S Christensen, Andreas Andersen, Anna Solini, Filip K Knop, Tina Vilsbøll
Along the obesity pandemic, the prevalence of non-alcoholic fatty liver disease (NAFLD), often regarded as the hepatic manifestation of the metabolic syndrome, increases worldwide representing now the prevalent liver disease in western countries. No pharmacotherapy is approved for the treatment of NAFLD and, currently, the cornerstone treatment is lifestyle modifications focusing on bodyweight loss, notoriously difficult to obtain and even more difficult to maintain. Thus, novel therapeutic approaches are highly demanded...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30456866/liraglutide-pharmacotherapy-reduces-body-weight-and-improves-glycemic-control-in-juvenile-obese-hyperglycemic-male-and-female-rats
#8
Claudia G Liberini, Rinzin Lhamo, Misgana Ghidewon, Tyler Ling, Nina Juntereal, Jack Chen, Anh Cao, Lauren M Stein, Matthew R Hayes
AIMS: Maternal and early-postnatal consumption of high-fat/high-sucrose diet (HFSD) dramatically alters the offspring phenotype, predisposing the progeny to have reduced sensitivity to satiation signals, increased body weight, and blood glucose impairments. Recent therapeutics for treating adult obesity have focused on targeting the glucagon-like-peptide-1 (GLP-1) system. Here, we examine whether the GLP-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/ hyperglycemia, but also prevent early-adult onset obesity...
November 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/30451975/periodontitis-affects-glucoregulatory-hormones-in-severely-obese-individuals
#9
Anna Solini, Jean Suvan, Eleonora Santini, Stefano Gennai, Marta Seghieri, Stefano Masi, Morena Petrini, Francesco D'Aiuto, Filippo Graziani
OBJECTIVE: To evaluate the effect of periodontitis (PD) on glucoregulatory hormones in obesity, never explored so far, a cross-sectional study was conducted in 110 severely obese, non-diabetic individuals. METHODS: We collected clinical periodontal parameters, including probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL). Insulin, glucagon, GLP-1 and GIP were measured after 3 days of standardized diet. RESULTS: Forty-seven subjects had periodontitis (PD+) and 63 did not (PD-)...
November 19, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/30445014/role-of-bile-acids-and-glp-1-in-mediating-the-metabolic-improvements-of-bariatric-surgery
#10
Vance L Albaugh, Babak Banan, Joseph Antoun, Yanhua Xiong, Yan Guo, Jie Ping, Muhammed Alikhan, Blake Austin Clements, Naji N Abumrad, Charles Robb Flynn
BACKGROUND AND AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, though parallel changes in body weight and other confounding variables limits this interpretation. METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5-/- ) and intestinal-specific farnesoid X receptor null (FxrΔ/E ) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/- ) mice on chow diet were characterized following bile diversion to the ileum (GB-IL)...
November 13, 2018: Gastroenterology
https://www.readbyqxmd.com/read/30430018/ileal-transposition-rapidly-improves-glucose-tolerance-and-gradually-improves-insulin-resistance-in-non-obese-type-2-diabetic-rats
#11
Hengliang Zhu, Huaiming Wang, Zhihai Zheng, Bailiang Ye, Xiaojiao Ruan, Xiaofeng Zheng, Guoxin Li
Background: Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus (T2DM), accompanied by increased glucagon-like peptide-1 (GLP-1). We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism. Methods: Twenty Goto-Kakizaki (GK) rats were randomly divided into the ileal transposition group (IT group) and the sham operation group (Sham group). Weight, food intake, fasting plasma glucose (FPG), fasting insulin (F-ins), oral glucose tolerance test (OGTT) and GLP-1 were determined at baseline and 1, 4, 8, 16 and 24 weeks post-operatively...
November 2018: Gastroenterology Report
https://www.readbyqxmd.com/read/30415909/combination-therapy-with-glucagon-like-peptide-1-receptor-agonists-and-sodium-glucose-cotransporter-2-inhibitors-in-older-patients-with-type-2-diabetes-a-real-world-evidence-study
#12
Juana Carretero Gómez, José Carlos Arévalo Lorido, Ricardo Gómez Huelgas, Dolores García de Lucas, Lourdes Mateos Polo, José Manuel Varela Aguilar, Jose Miguel Seguí Ripoll, Javier Ena
OBJECTIVES: Scientific literature about the combination of glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients is scarce. We sought to assess the real-world efficacy and safety of SGLT2 inhibitors and GLP-1ra combination therapy in older patients (>65 years of age). METHODS: This was an observational, prospective, multicenter study based on clinical practice. Patients were stratified according to tertiles of baseline glycated hemoglobin (A1C) levels and to treatment schedule...
September 8, 2018: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/30400947/impact-of-rye-based-evening-meals-on-cognitive-functions-mood-and-cardiometabolic-risk-factors-a-randomized-controlled-study-in-healthy-middle-aged-subjects
#13
Jonna C Sandberg, Inger M E Björck, Anne C Nilsson
BACKGROUND: Whole grain (WG) intake is associated with reduced risk of obesity, type 2 diabetes and cardiovascular disease, whereas type 2 diabetes increases the risk of cognitive decline and dementia. The purpose of this study was to investigate the effects of short-term intervention with WG rye on cognitive functions, mood and cardiometabolic risk markers in middle-aged test subjects. METHOD: Rye-based breads were provided to 38 healthy test subjects (aged 52-70y) during three consecutive days in a crossover study design, using white wheat flour bread (WWB) as a reference...
November 6, 2018: Nutrition Journal
https://www.readbyqxmd.com/read/30371047/treating-prediabetes-why-and-how-should-we-do-it
#14
Tassia Braga, Luiz G Kraemer-Aguiar, Neil Docherty, Carel Le Roux
INTRODUCTION: Prediabetes is the subclinical impairment in fasting plasma glucose, impaired glucose tolerance or both. The degree of impairment is between euglycemia and the hyperglycemia of Type 2 Diabetes. EVIDENCE ACQUISITION: Prediabetes is not considered benign, because it is a risk factor for Type 2 Diabetes but is also associated with micro and macrovascular complications. Lifestyle interventions including diet and exercise are first-line treatments. Medications can also play a role, as randomized controlled trials of alpha-glucosidase inhibitors (Acarbose), inhibitors of pancreatic lipase (Orlistat), PPAR-gamma agonists (Rosiglitazone, Pioglitazone), meglitinides (Nateglinide) and GLP-1 receptor agonists (Liraglutide) have all shown benefits...
October 29, 2018: Minerva Medica
https://www.readbyqxmd.com/read/30315341/postprandial-hypoglycaemia-after-roux-en-y-gastric-bypass-in-individuals-with-type-2-diabetes
#15
Daniela Guarino, Diego Moriconi, Andrea Mari, Eleni Rebelos, Daria Colligiani, Simona Baldi, Marco Anselmino, Ele Ferrannini, Monica Nannipieri
AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery...
October 12, 2018: Diabetologia
https://www.readbyqxmd.com/read/30305366/pancreatic-%C3%AE-cell-rest-replenishes-insulin-secretory-capacity-and-attenuates-diabetes-in-an-extreme-model-of-obese-type-2-diabetes
#16
Brandon B Boland, Charles Brown, Michelle L Boland, Jennifer Cann, Michael Sulikowski, Gitte Hansen, Rikke V Grønlund, Wanda King, Cristina Rondinone, James Trevaskis, Christopher J Rhodes, Joseph S Grimsby
The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic β-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the β-cell deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on β-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity following treatment with thiazolidinedione (TZD) therapy or glucagon-like-peptide-1 receptor (GLP-1R) agonism alone, or in combination with sodium/glucose cotransporter-2 inhibition (SGLT-2i)...
October 10, 2018: Diabetes
https://www.readbyqxmd.com/read/30296922/novel-insights-into-the-dynamics-behavior-of-glucagon-like-peptide-1-receptor-with-its-small-molecule-agonists
#17
Khyati Girdhar, Budheswar Dehury, Mahender Kumar Singh, Vineeth P Daniel, Abhinav Choubey, Surbhi Dogra, Sunil Kumar, Prosenjit Mondal
The glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of therapeutics industries for the treatment of various metabolic diseases like Type2 Diabetes and Obesity. The structural-functional relationships of small molecule agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R. In this study, we explored the dynamics, intrinsic stability and binding mechanisms of these molecules through computational modeling, docking, molecular dynamics (MD) simulations and MM/PBSA binding free energy estimation...
October 8, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/30291106/management-of-hyperglycemia-in-type-2-diabetes-2018-a-consensus-report-by-the-american-diabetes-association-ada-and-the-european-association-for-the-study-of-diabetes-easd
#18
Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended...
October 4, 2018: Diabetes Care
https://www.readbyqxmd.com/read/30288571/management-of-hyperglycaemia-in-type-2-diabetes-2018-a-consensus-report-by-the-american-diabetes-association-ada-and-the-european-association-for-the-study-of-diabetes-easd
#19
Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended...
December 2018: Diabetologia
https://www.readbyqxmd.com/read/30250193/restoration-of-glp-1-secretion-by-berberine-is-associated-with-protection-of-colon-enterocytes-from-mitochondrial-overheating-in-diet-induced-obese-mice
#20
Yongning Sun, Chenxi Jin, Xiaoying Zhang, Weiping Jia, Jiamei Le, Jianping Ye
OBJECTIVE: L-cell dysfunction is reported for GLP-1 reduction in type 2 diabetes. However, the mechanism of dysfunction remains unknown. In this study, we examined mitochondrial function in the mechanistic study in diet-induced obese (DIO) mice. SUBJECTS: C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks to establish the DIO model for GLP-1 reduction. The mice were then treated with berberine (BBR) (100 mg/kg/day) for 8 weeks to test the impact on GLP-1 expression...
September 24, 2018: Nutrition & Diabetes
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