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https://www.readbyqxmd.com/read/27934480/a-mechanistic-study-on-nanoparticle-mediated-glucagon-like-peptide-1-glp-1-secretion-from-enteroendocrine-l-cells
#1
Ana Beloqui, Mireille Alhouayek, Dario Carradori, Kevin Vanvarenberg, Giulio G Muccioli, Patrice D Cani, Véronique Préat
L cells have attracted particular interest because of the pleiotropic effects of their secreted peptides (i.e., glucagon-like peptide (GLP) 1 and 2, peptide YY (PYY)). L cells express different G-protein-coupled receptors (GPCRs) that can be activated by endogenous ligands found in the gut lumen. We herein hypothesized that lipid-based nanoparticles could mimic endogenous ligands and thus activate GLP-1 secretion in type 2 diabetes mellitus treatment. To assess this hypothesis, lipid-based nanoparticles (nanostructured lipid carriers (NLC), lipid nanocapsules (LNC), and liposomes) and PLGA nanoparticles were added to the L cells and GLP-1 secretion was quantified...
December 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27933334/improved-glycaemia-in-high-fat-fed-neprilysin-deficient-mice-is-associated-with-reduced-dpp-4-activity-and-increased-active-glp-1-levels
#2
Joshua R Willard, Breanne M Barrow, Sakeneh Zraika
AIM/HYPOTHESIS: Neprilysin, a widely expressed peptidase, is upregulated in metabolically altered states such as obesity and type 2 diabetes. Like dipeptidyl peptidase-4 (DPP-4), neprilysin can degrade and inactivate the insulinotropic peptide glucagon-like peptide-1 (GLP-1). Thus, we investigated whether neprilysin deficiency enhances active GLP-1 levels and improves glycaemia in a mouse model of high fat feeding. METHODS: Nep (+/+) and Nep (-/-) mice were fed a 60% fat diet for 16 weeks, after which active GLP-1 and DPP-4 activity levels were measured, as were glucose, insulin and C-peptide levels during an OGTT...
December 8, 2016: Diabetologia
https://www.readbyqxmd.com/read/27930863/lessons-from-a-cardiovascular-outcome-trial-with-liraglutide-in-type-2-diabetes
#3
Hae Jin Kim, Dae Jung Kim
Cardiovascular disease (CVD) is the leading cause of death and one of common diabetes-related complications in patients with type 2 diabetes(1) . After the US Food and Drug Administration issued guidelines for assessing the CVD risk of all new glucose-lowering agents for type 2 diabetes in 2008(2) , randomized controlled CV outcome trials with new antidiabetic drugs, such as the dipeptidyl peptidase-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) and the glucagon-like peptide-1 receptor agonist (GLP-1 RA), lixisenatide, showed CV safety in high CV risk patient populations with type 2 diabtes(3) ...
December 8, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27930690/structural-mapping-and-functional-characterization-of-zebrafish-class-b-g-protein-coupled-receptor-gpcr-with-dual-ligand-selectivity-towards-glp-1-and-glucagon
#4
Deena A Oren, Yang Wei, Luce Skrabanek, Billy K C Chow, Thomas Mommsen, Svetlana Mojsov
GLP-1 and glucagon regulate glucose metabolism through a network of metabolic pathways initiated upon binding to their specific receptors that belong to class B G-protein coupled receptors (GPCRs). The therapeutic potential of glucagon is currently being evaluated, while GLP-1 is already used in the treatment of type 2 diabetes and obesity. Development of a second generation of GLP-1 based therapeutics depends on a molecular and structural understanding of the interactions between the GLP-1 receptor (GLP-1R) and its ligand GLP-1...
2016: PloS One
https://www.readbyqxmd.com/read/27929679/glp-1-analogues-for-the-treatment-of-type-2-diabetes-in-latinos-hispanics
#5
A Enrique Caballero
No abstract text is available yet for this article.
December 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27928844/glucagon-like-peptide-1-receptor-expression-on-human-eosinophils-and-its-regulation-of-eosinophil-activation
#6
Patrick D Mitchell, Brittany M Salter, John Paul Oliveria, Amani El-Gammal, Damian Tworek, Steve G Smith, Roma Sehmi, Gail M Gauvreau, Marcus Butler, Paul M O'Byrne
BACKGROUND: Glucagon Like Peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones the regulate glucose metabolism. GLP-1 also has immune modulatory roles. OBJECTIVES: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. METHODS: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects...
December 8, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27924636/safety-and-tolerability-of-glucagon-like-peptide-1-receptor-agonists-unresolved-and-emerging-issues
#7
Denis Raccah
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for Type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and can be used alone or in combination with other antidiabetic agents. Based on the duration of their effects, GLP-1 RAs can be divided into two classes: short-acting and long-acting. Differences exist between these sub-classes, and between each drug, in terms of pharmacokinetic and pharmacodynamic profiles...
December 7, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27922176/dipeptidyl-peptidase-4-inhibitor-sitagliptin-reduces-inflammation-fibrosis-and-preserves-diastolic-function-in-a-rat-model-of-heart-failure-with-preserved-ejection-fraction
#8
Grazia Esposito, Donato Cappetta, Rosa Russo, Alessia Rivellino, Loreta Pia Ciuffreda, Fiorentina Roviezzo, Elena Piegari, L Liberato Berrino, Francesco Rossi, Antonella De Angelis, Konrad Urbanek
BACKGROUND AND PURPOSE: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome driven by co-morbidities and its pathophysiology is poorly understood. Several studies suggesting that dipeptidyl peptidase 4 (DPP4) might be involved in the pathophysiology of heart failure prompted experimental and clinical investigations of DPP4 inhibitors on cardiovascular system. The aim of our study was to determine whether DPP4 inhibitor sitagliptin (SITA) affects the progression of HFpEF independently from the effects on glycaemia...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#9
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27916475/effects-of-polydextrose-with-breakfast-or-with-a-midmorning-preload-on-food-intake-and-other-appetite-related-parameters-in-healthy-normal-weight-and-overweight-females-an-acute-randomized-double-blind-placebo-controlled-and-crossover-study
#10
Alvin Ibarra, Kaisa Olli, Wilrike Pasman, Henk Hendriks, Esa Alhoniemi, Ghulam Shere Raza, Karl-Heinz Herzig, Kirsti Tiihonen
Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females...
December 1, 2016: Appetite
https://www.readbyqxmd.com/read/27915035/hyperinsulinaemic-hypoglycaemia-in-children-and-adults
#11
REVIEW
Pratik Shah, Sofia A Rahman, Huseyin Demirbilek, Maria Güemes, Khalid Hussain
Pancreatic β cells are functionally programmed to release insulin in response to changes in plasma glucose concentration. Insulin secretion is precisely regulated so that, under normal physiological conditions, fasting plasma glucose concentrations are kept within a narrow range of 3·5-5·5 mmol/L. In hyperinsulinaemic hypoglycaemia, insulin secretion becomes dysregulated (ie, uncoupled from glucose metabolism) so that insulin secretion persists in the presence of low plasma glucose concentrations. Hyperinsulinaemic hypoglycaemia is the most common cause of severe and persistent hypoglycaemia in neonates and children...
November 30, 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27913575/lowest-glucose-variability-and-hypoglycemia-are-observed-with-the-combination-of-a-glp-1-receptor-agonist-and-basal-insulin-variation-study
#12
Harpreet S Bajaj, Karri Venn, Chenglin Ye, Avril Patrick, Shivani Kalra, Hasnain Khandwala, Nadeem Aslam, David Twum-Barima, Ronnie Aronson
OBJECTIVE: There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB). RESEARCH DESIGN AND METHODS: Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m(2), stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7...
December 2, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27912784/liraglutide-improves-metabolic-parameters-and-carotid-intima-media-thickness-in-diabetic-patients-with-the-metabolic-syndrome-an-18-month-prospective-study
#13
Manfredi Rizzo, Ali A Rizvi, Angelo Maria Patti, Dragana Nikolic, Rosaria Vincenza Giglio, Giuseppa Castellino, Giovanni Li Volti, Massimiliano Caprio, Giuseppe Montalto, Vincenzo Provenzano, Stefano Genovese, Antonio Ceriello
BACKGROUND: Liraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM. METHODS: We performed an 18-month prospective, real-world study...
December 3, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27908915/-the-hypothalamic-glucagon-like-peptide-1-glp-1-receptor-glp-1r-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#14
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27908836/gq-and-gs-signaling-acting-in-synergy-to-control-glp-1-secretion
#15
Maria Hauge, Jeppe Pio Ekberg, Maja Storm Engelstoft, Pascal Timshel, Andreas N Madsen, Thue W Schwartz
GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27904405/evaluation-of-prebiotic-effects-of-high-purity-galactooligosaccharides-in-vitro-and-in-vivo
#16
Ki Bae Hong, Jae Hwan Kim, Hyuk Kon Kwon, Sung Hee Han, Yooheon Park, Hyung Joo Suh
Galactooligosaccharides (GOS) are an important class of dietary prebiotics that exert beneficial effects on intestinal microbiota and gut barrier function. In this study, high-purity GOS (HP-GOS) were investigated in vitro and in vivo and confirmed as prebiotic ingredients in rat diet. HP-GOS were successfully produced using a two-step process, enzymatic hydrolysis and fermentation by yeast. They were found to serve as a good substrate and carbon source for supporting the growth of probiotic bacteria more effectively than other commercial GOS...
June 2016: Food Technology and Biotechnology
https://www.readbyqxmd.com/read/27900077/selective-beneficial-cardiometabolic-effects-of-vertical-sleeve-gastrectomy-are-predominantly-mediated-through-glucagon-like-peptide-glp-1-in-zucker-diabetic-fatty-rats
#17
Sunil Kumar, Raymond Lau, Thomas Palaia, Christopher Hall, Jenny Lee, Keneth Hall, Collin E Brathwaite, Louis Ragolia
BACKGROUND: Glucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects. OBJECTIVE: To validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats. METHODS: Animals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9-39 (GLP-1 receptor antagonist)...
December 2016: Annals of Medicine and Surgery
https://www.readbyqxmd.com/read/27898108/monotreme-glucagon-like-peptide-1-in-venom-and-gut-one-gene-two-very-different-functions
#18
Enkhjargal Tsend-Ayush, Chuan He, Mark A Myers, Sof Andrikopoulos, Nicole Wong, Patrick M Sexton, Denise Wootten, Briony E Forbes, Frank Grutzner
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894746/roux-en-y-gastric-bypass-versus-calorie-restriction-support-for-surgery-per-se-as-the-direct-contributor-to-altered-responses-of-insulin-and-incretins-to-a-mixed-meal
#19
Johan Berggren, Andreas Lindqvist, Jan Hedenbro, Leif Groop, Nils Wierup
OBJECTIVE: To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR). SETTING: University-affiliated bariatric surgery clinic. BACKGROUND: RYGB induces remission of type 2 diabetes (T2D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic...
September 28, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27892685/gut-a-key-player-in-the-pathogenesis-of-type-2-diabetes
#20
Giovanna Muscogiuri, Giancarlo Balercia, Luigi Barrea, Angelo Cignarelli, Francesco Giorgino, Jens J Holst, Daniela Laudisio, Francesco Orio, Giacomo Tirabassi, Annamaria Colao
The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes...
November 28, 2016: Critical Reviews in Food Science and Nutrition
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