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Glucagon-like peptide

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https://www.readbyqxmd.com/read/28828521/recombinant-lactococcus-lactis-expressing-bioactive-exendin-4-to-promote-insulin-secretion-and-beta-cell-proliferation-in-vitro
#1
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Huiqin Ma, Shangwu Chen
In recent years, therapeutic peptides have garnered great interest in the pharmaceutical industry for the treatment of diabetes. Lactic acid bacteria (LAB) are an appealing vehicle for safe and convenient oral delivery of bioactive peptide and protein drugs. Exendin-4 (Exd4) is a glucagon-like protein-1 (GLP-1) receptor agonist that is considered an excellent therapeutic peptide drug for type 2 diabetes due to its longer-lasting bioactivity, resulting from resistance to dipeptidyl peptidase 4. We explored Lactococcus lactis with the nisin-controlled gene expression (NICE) system as an oral delivery system for recombinant (r) Exd4 peptide in situ...
August 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28827024/gastrointestinal-adverse-events-of-dipeptidyl-peptidase-4-inhibitors-in-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#2
Shanshan Wu, Sanbao Chai, Jun Yang, Ting Cai, Yang Xu, Zhirong Yang, Yuan Zhang, Linong Ji, Feng Sun, Siyan Zhan
PURPOSE: The purpose of this study was to systematically evaluate the effect of dipeptidyl peptidase 4 inhibitors on gastrointestinal adverse events in patients with type 2 diabetes. METHODS: MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception through April 28, 2016. Randomized controlled trials that compared dipeptidyl peptidase 4 inhibitor-based therapies with placebo and other hypoglycemic agents in type 2 diabetes were included...
August 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#3
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
August 19, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28822777/managing-the-course-of-diabetic-kidney-disease-from-the-old-to-the-new
#4
REVIEW
Ronald M Goldenberg, Murray Berall, Christopher T M Chan, David Z I Cherney, Julie A Lovshin, Philip A McFarlane, Peter A Senior, Subodh Verma, Jordan J Weinstein
Diabetic kidney disease (DKD) is a group of chronic kidney diseases that is associated with significant cardiovascular as well as all-cause morbidity and mortality. Although DKD is often progressive in nature, its evolution can be modified by intensive management of glycemia and blood pressure and inhibition of the renin-angiotensin-aldosterone system. This review provides an overview of how multifactorial interventions can provide renal protection and includes a discussion of the nonglycemic effects of incretin-based diabetes therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors) and sodium-glucose cotransporter-2 inhibitors within the kidney in patients with type 2 diabetes...
August 16, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28818558/current-and-emerging-pharmacotherapies-for-obesity-in-australia
#5
REVIEW
Samantha Hocking, Anthony Dear, Michael A Cowley
BACKGROUND: Obesity is a major issue in Australia and globally. Many individuals struggle to maintain weight loss with lifestyle modification, and adjunctive pharmacotherapy may help. Historically, there have been limited pharmacotherapies for managing obesity. In addition, previous treatments such as phentermine-fenfluramine, rimonabant and sibutramine were withdrawn due to safety issues, resulting in lingering safety concerns. METHODS: This is a narrative review of published data examining four new pharmacotherapy options for weight management in Australia...
August 14, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28816532/comparing-clinical-outcomes-and-costs-for-different-treatment-intensification-approaches-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin-adding-glucagon-like-peptide-1-receptor-agonists-vs-adding-rapid-acting-insulin-or-increasing-basal-insulin
#6
Philip Levin, Tao Fan, Xue Song, Damion Nero, Brian Davis, Bong-Chul Chu
Objective-Not all patients with type 2 diabetes achieve the recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes. Methods-This retrospective analysis of health insurance claims data in the US MarketScan database compared glycemic control and healthcare resource utilization and costs 12 months after adding GLP-1 RA to BI vs adding RAI or increasing BI doses...
August 17, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#7
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28811669/paraventricular-thalamic-control-of-food-intake-and-reward-role-of-glucagon-like-peptide-1-receptor-signaling
#8
Zhi Yi Ong, Jing-Jing Liu, Zhiping P Pang, Harvey J Grill
Paraventricular thalamic nucleus (PVT) neurons receive hindbrain and hypothalamic inputs, and project to forebrain sites involved in reward and motivation function. The role of PVT in energy balance and reward control is however understudied. Given that PVT neurons express glucagon-like peptide-1 receptors (GLP-1R), which are critical to feeding and body weight control, we tested the hypothesis that PVT GLP-1R signaling contributes to food intake and reward inhibition. To assess the hypothesis, behavioral tests including chow and high-fat diet intake, meal patterns, conditioned place preference for high-fat food, cue-induced reinstatement of sucrose-seeking, and motivation to work for sucrose were employed following intra-PVT delivery of either GLP-1R agonist, exendin-4 (Ex4), or GLP-1R antagonist, exendin-9-39 (Ex9)...
July 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#9
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28808865/glucagon-like-peptides-1-and-2-are-involved-in-satiety-modulation-after-modified-biliopancreatic-diversion-results-of-a-pilot-study
#10
Everton Cazzo, José Carlos Pareja, Elinton Adami Chaim, Cláudio Saddy Rodrigues Coy, Daniéla Oliveira Magro
BACKGROUND: This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation. METHODS: This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS)...
August 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28808291/glp-1-inhibits-high-glucose-induced-oxidative-injury-of-vascular-endothelial-cells
#11
Quan Li, Yajun Lin, Shu Wang, Lina Zhang, Lixin Guo
The aim of this work was to evaluate the effects of glucagon-like peptide-1 (GLP-1) on high-glucose-induced oxidative stress and investigate the possible mechanisms underlying this process. We measured reactive oxygen species (ROS) production, cell apoptosis, the expression of NOX4 and its subunits, and p47phox translocation in human umbilical vein endothelial cells (HUVECs). An experimental type 2 diabetes model was induced using streptozotocin in male Sprague-Dawley rats. Fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and free fatty acid (FFA) were measured...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807775/the-potential-benefits-of-glucagon-like-peptide-1-receptor-agonists-for-diabetic-retinopathy
#12
REVIEW
Baoying Pang, Huanran Zhou, Hongyu Kuang
For a long time, diabetic retinopathy (DR) has been one of the most severe complications of diabetes. The early treatment of DR is not clearly recognized. The additional benefit of hypoglycemic agents for DR has become a new research field. Glucagon-like peptide-1 receptor (GLP-1R) has been shown to be widely expressed in tissues including retina. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been generally used in the treatment of diabetic patients. Studies shows that GLP-1RA could inhibit nerve damage by decrease apoptosis of nerve cells and activation of glial cells...
August 11, 2017: Peptides
https://www.readbyqxmd.com/read/28807218/teduglutide-effects-on-gene-regulation-of-fibrogenesis-on-an-animal-model-of-intestinal-anastomosis
#13
Beatriz P Costa, Ana C Gonçalves, Ana M Abrantes, Paulo Matafome, Raquel Seiça, Ana B Sarmento-Ribeiro, Maria Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Teduglutide is an enterotrophic analog of glucagon-like peptide 2 approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the effects of teduglutide administration on the gene regulation of fibrogenesis during the intestinal anastomotic healing on an animal model. METHODS: Wistar rats (n = 62) were assigned into four groups: "Ileal Resection and Anastomosis" or "Laparotomy," each one subdivided into "Postoperative Teduglutide Administration" or "No Treatment," and sacrificed at the third or at the seventh days, with ileal sample harvesting...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28805670/appetite-and-gut-hormones-response-to-a-putative-%C3%AE-glucosidase-inhibitor-salacia-chinensis-in-overweight-obese-adults-a-double-blind-randomized-controlled-trial
#14
Lihong Hao, Yvette Schlussel, Krista Fieselmann, Stephen H Schneider, Sue A Shapses
Animal studies indicate Salacia reduces body weight, possibly due to its α-glucosidase inhibitor (α-GI) properties, but this has not been examined previously. In this study, a randomized, placebo-controlled, three-way cross-over design was used to evaluate whether Salacia Chinensis (SC) reduces appetite in healthy overweight/obese individuals (body mass index 28.8 ±3.6 kg/m²; 32 ± 12 years). Forty-eight participants were fasted overnight and consumed a dose of SC (300 or 500 mg) or placebo with a fixed breakfast meal at each visit...
August 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28803984/canagliflozin-potentiates-glp-1-secretion-and-lowers-the-peak-of-gip-secretion-in-rats-fed-a-high-fat-high-sucrose-diet
#15
Tohru Hira, Toshiki Koga, Kazuyo Sasaki, Hiroshi Hara
The glucose-induced secretion of incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), is dependent on luminal glucose levels and transport of glucose via the sodium-glucose transporter 1 (SGLT1) in the small intestine. Because GLP-1 and GIP function in decreasing and increasing the body weight, respectively, we aimed to analyze the effect of transient inhibition of SGLT1 by canagliflozin on incretin secretion in an obese rat model. Male Sprague-Dawley rats were maintained on a high-fat high-sucrose diet for 6-7 weeks, and plasma GLP-1 and GIP levels were measured using an oral glucose tolerance test (OGTT)...
August 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#16
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801475/understanding-the-gap-between-efficacy-in-randomized-controlled-trials-and-effectiveness-in-real-world-use-of-glp-1ra-and-dpp4-therapies-in-patients-with-type-2-diabetes
#17
Ginger S Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V Edelman, William H Polonsky
OBJECTIVE: This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs...
August 11, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28800948/comparative-effects-of-intraduodenal-fat-and-glucose-on-the-gut-incretin-axis-in-healthy-males
#18
Tongzhi Wu, Christopher K Rayner, Linda E Watson, Karen L Jones, Michael Horowitz, Tanya J Little
BACKGROUND: The interaction of nutrients with the small intestine stimulates the secretion of numerous enteroendocrine hormones that regulate postprandial metabolism. However, differences in gastrointestinal hormonal responses between the macronutrients are incompletely understood. In the present study, we compared blood glucose and plasma hormone concentrations in response to standardised intraduodenal (ID) fat and glucose infusions in healthy humans. METHODS: In a parallel study design, 16 healthy males who received an intraduodenal fat infusion were compared with 12 healthy males who received intraduodenal glucose, both at a rate of 2kcal/min over 120min...
August 8, 2017: Peptides
https://www.readbyqxmd.com/read/28800417/buccal-delivery-of-small-molecules-and-biologics-of-mucoadhesive-polymers-films-and-nanoparticles
#19
REVIEW
Javier O Morales, David J Brayden
Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics...
August 8, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28800090/the-effect-of-buffering-high-acid-load-meal-with-sodium-bicarbonate-on-postprandial-glucose-metabolism-in-humans-a-randomized-placebo-controlled-study
#20
Pinar Kozan, Jackson C Blythe, Jerry R Greenfield, Dorit Samocha-Bonet
Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants (n = 32) were randomized to receive either 1680 mg NaHCO₃ or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1-4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C-peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15-30 min intervals for 3 h post meal...
August 11, 2017: Nutrients
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