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https://www.readbyqxmd.com/read/29144968/a-synaptic-basis-for-glp-1-action-in-the-brain
#1
Sandrine Lefort, Matthias H Tschöp, Cristina García-Cáceres
Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. (2017) identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#2
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29138359/comparative-effects-of-intraduodenal-amino-acid-infusions-on-food-intake-and-gut-hormone-release-in-healthy-males
#3
Robert E Steinert, Sina S Ullrich, Nori Geary, Lori Asarian, Marco Bueter, Michael Horowitz, Christine Feinle-Bisset
In contrast to the many studies of the effects of individual amino acids (AAs) on eating, no studies have compared the effects of different AAs on eating and underlying preabsorptive gastrointestinal mechanisms. To compare the effects of intraduodenal infusions of l-tryptophan (TRP), l-leucine (LEU), l-phenylalanine (PHE) and l-glutamine (GLN) on appetite, gastrointestinal hormone responses (including ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 [GLP-1]), glycemia (glucagon, insulin and glucose) and test meal size in healthy males, we retrospectively analyzed data from four published independent, randomized, double-blind, placebo-controlled studies of 90-min intraduodenal infusions of the individual AAs...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29138226/insulin-secretory-effect-of-sitagliptin-assessment-with-a-hyperglycemic-clamp-combined-with-a-meal-challenge
#4
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Helmut O Steinberg, Chan R Beals, David E Kelley
Sitagliptin,a dipeptidylpeptidase-IVinhibitor(DPP-4),sustains activity of the incretin hormones GLP-1andGIP and improves hyperglycemia inT2DM.It has however proven challenging to quantify the effect of sitagliptin on rates of insulin secretion(ISR) during a prandial challenge.The tight feedback governance ofISR by plasma glucose means that in the face of treatment-related lowering of postprandialglycemia,corresponding stimulation ofISR is lessened.We postulated that sustaining a stable level of moderate hyperglycemia prior to and during a mealchallenge(MC)would be a platform that enables greater clarity to assess the effect ofsitagliptin onISR and an approach that could be valuable to evaluate novel targets that increase insulin secretion directly and by augmenting incretins...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29137984/recombinant-human-glp-1-rhglp-1-alleviating-renal-tubulointestitial-injury-in-diabetic-stz-induced-rats
#5
Weiqin Yin, Shiqing Xu, Zai Wang, Honglin Liu, Liang Peng, Qing Fang, Tingting Deng, Wenjian Zhang, Jinning Lou
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137471/serum-levels-of-spexin-and-kisspeptin-negatively-correlate-with-obesity-and-insulin-resistance-in-women
#6
P A Kołodziejskii, E Pruszyńska-Oszmałek, E Korek, M Sassek, D Szczepankiewicz, P Kaczmarek, L Nogowski, P Maćkowiak, K W Nowak, H Krauss, M Z Strowski
Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29135069/impaired-secretion-of-active-glp-1-in-patients-with-hypertriglyceridaemia-a-novel-lipotoxicity-paradigm
#7
Xiangxiang Wang, Jia Liu, Chaolin Li, Meng Zhao, Lu Liu, Qingbo Guan, Haiqing Zhang, Xu Zhang, Ling Gao, Jiajun Zhao, Yongfeng Song
AIM: Lipotoxicity plays an important role in the pathogenesis of β-cell dysfunction. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that exerts beneficial effects on the number and function of islet β cells. However, the effect of lipotoxicity on GLP-1 secretion is still unknown. METHODS: Twenty-five patients who were newly diagnosed with diabetes were recruited from 400 subjects based on 75 g Oral Glucose Tolerance Test (OGTT). Patients were divided into diabetes (DM) and DM combined with hypertriglyceridaemia (DM+HTG) groups according to their serum triglyceride (TG) levels...
November 14, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29134607/the-cost-effectiveness-of-dulaglutide-1-5mg-versus-exenatide-qw-for-the-treatment-of-patients-with-type-2-diabetes-mellitus-in-france
#8
Mickael Basson, Dionysios Ntais, Ruba Ayyub, Donna Wright, Julia Lowin, Florence Chartier, Stéphane Roze, Kirsi Norrbacka
INTRODUCTION: Dulaglutide is a novel onceweekly administered glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the management of type 2 diabetes mellitus (T2DM). The objective of this analysis was to estimate the cost-effectiveness of dulaglutide 1.5 mg versus exenatide QW for the management of T2DM in France. METHODS: The QuintilesIMS CORE Diabetes Model was used to estimate the expected lifetime direct medical costs and outcomes of T2DM from the perspective of the French National Health Service...
November 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29133778/glucagon-like-peptide-1-glp-1-receptor-agonist-liraglutide-alters-bone-marrow-exosome-mediated-mirna-signal-pathways-in-ovariectomized-rats-with-type-2-diabetes
#9
Jin Li, Ling-Zhi Fu, Lu Liu, Fen Xie, Ru-Chun Dai
BACKGROUND Compared with normal postmenopausal women, estrogen deficiency and hyperglycemia in postmenopausal women with type 2 diabetes (T2DM) lead to more severe bone property degradation. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been reported to improve bone condition among people with T2DM but the precise mechanisms remain unclear. Exosomes work as mediators in cell-to-cell communication, delivering functional miRNAs between cells. We aimed to explore the role of exosomes in T2DM-related bone metabolic disorders and the bone protective mechanisms of liraglutide...
November 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29132091/effect-of-anti-diabetic-drugs-on-bone-metabolism-evidence-from-preclinical-and-clinical-studies
#10
REVIEW
Mohammad Adil, Rashid Ali Khan, Abul Kalam, Shiva Kumar Venkata, Amit Dattatraya Kandhare, Pinaki Ghosh, Manju Sharma
Diabetes mellitus is associated with abnormal bone health and an increased risk of fracture even though patients have normal or higher BMD. The mechanisms behind diabetes mellitus- induced various skeletal disorders remain unclear. Anti-diabetic drugs may have negative or positive impact on bone metabolism. For instance, thiazolidinediones increases the bone loss and risk of fracture possibly through PPARγ activation in bone marrow cells and hamper osteoblastogenesis via decreasing Runx2 transcription factor, IGF-1 and Wnt signalling pathways...
May 25, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#11
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29129776/glucagon-like-peptide-1-glp-1-and-neurotransmitters-signaling-in-epilepsy-an-insight-review
#12
REVIEW
Prashant Koshal, Sumit Jamwal, Puneet Kumar
Epilepsy is one of the most prevalent neurological disorder affecting more than 50 million people worldwide. Numerous studies have suggested that an imbalance in glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmitter system is one of the dominating pathophysiological mechanisms underlying the occurrence and progression of seizures. Further, this alteration in GABAergic and glutamatergic system disrupts the delicate balance of other neurotransmitters system in the brain. Emerging strides have documented the protective role of GLP-1 signaling on altered neurotransmitters signaling in Epilepsy and associated co-morbidities...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29129645/incretins-modulate-progesterone-biosynthesis-by-regulating-bone-morphogenetic-protein-activity-in-rat-granulosa-cells
#13
Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of incretins on ovarian steroidogenesis have not been clarified. In this study, we investigated the effects of incretins, including GIP and GLP-1, on ovarian steroidogenesis using rat primary granulosa cells. Treatment with incretins significantly suppressed progesterone synthesis in the presence of FSH, and the effect of GIP was more potent than that of GLP-1. In contrast, incretins had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of incretins on steroidogenesis, GIP and GLP-1 suppressed the expression of progesterogenic factors and enzymes, including StAR, P450scc, 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
November 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29128557/the-effect-of-diet-adiposity-and-weight-loss-on-the-secretion-of-incretin-hormones-in-cats
#14
K E McCool, A J Rudinsky, V J Parker, C O Herbert, C Gilor
Degree of adiposity and dietary macronutrient composition affect incretin hormone secretion in humans and mice, but little is known about their effect in cats. In this study, 7 overweight cats were fed a maintenance diet (MD) for at least 2 wk followed by a reduced calorie diet (RCD), which was lower in fat and higher in carbohydrates and fiber. Cats were fed ad libitum initially, and then, food was restricted to achieve 1%-2% loss of body weight weekly (11 wk). When lean, cats were fed MD for 2 wk. A standardized meal test (SMT) using a third diet was performed after at least 7 d on each diet, before and after weight loss (four SMT's total)...
October 20, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29128339/rs6923761-gene-variant-in-glucagon-like-peptide-1-receptor-allelic-frequencies-and-influence-on-cardiovascular-risk-factors-in-a-multicenter-study-of-castilla-leon
#15
D A de Luis, M Ballesteros, A Lopez Guzman, E Ruiz, C Muñoz, M A Penacho, P Iglesias, A Maldonado, V Puigdevall, M Delgado
BACKGROUND: Some GLP-1 receptor studies have identified polymorphisms in the GLP-1 receptor gene that might be related to different cardiovascular risk factors. OBJECTIVE: Our aim was to investigate the allelic distribution of rs6923761 GLP-1 receptor polymorphism in a geographic area of Spain (Community of Castilla y Leon) and to evaluate the influence of this polymorphism on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese patients...
November 2, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29121068/metabolic-regulation-of-glp-1-and-pc1-3-in-pancreatic-%C3%AE-cell-line
#16
Veronica Sancho, Giuseppe Daniele, Daniela Lucchesi, Roberto Lupi, Annamaria Ciccarone, Giuseppe Penno, Cristina Bianchi, Angela Dardano, Roberto Miccoli, Stefano Del Prato
BACKGROUND AND AIMS: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia. MATERIALS AND METHODS: AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5...
2017: PloS One
https://www.readbyqxmd.com/read/29120673/standard-curves-are-necessary-to-determine-pharmacological-properties-for-ligands-in-functional-assays-using-competition-binding-technologies
#17
Neil T Burford, John Watson, Andrew Alt
Homogeneous functional assays that utilize competition binding technology are widely used for determining pharmacological properties such as intrinsic activity and potency. One example is time-resolved fluorescence resonance energy transfer (TR-FRET) 3',5'-cyclic adenosine monophosphate (cAMP) assays, where labeled cAMP (tracer) and a labeled anti-cAMP antibody bind together to produce a TR-FRET signal when the two constituents are proximal to each other. This signal is disrupted when unlabeled and cellularly generated cAMP competes with the tracer cAMP for binding to the labeled antibody...
October 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29119712/impact-of-delaying-treatment-intensification-with-a-glucagon-like-peptide-1-receptor-agonist-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin-a-longitudinal-study-of-a-us-administrative-claims-database
#18
L Tong, C Pan, H Wang, M Bertolini, E Lew, L F Meneghini
AIM: To evaluate the effect of delaying treatment intensification with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) on clinical and economic outcomes in patients with type 2 diabetes (T2D). METHODS: We conducted a retrospective observational claims study using IMPACT(TM) , in adult patients with T2D who initiated basal insulin between 1 January 2005 and 31 December 2012 with or without OADs, but remained uncontrolled (glycated haemoglobin [HbA1c] ≥7.0%)...
November 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#19
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29118282/the-role-of-bile-acids-in-glucose-metabolism-and-their-relation-with-diabetes
#20
José Alberto González-Regueiro, Lidia Moreno-Castañeda, Misael Uribe, Norberto C Chávez-Tapia
Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure...
October 4, 2017: Annals of Hepatology
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