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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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/28801845/accurate-analytical-method-for-human-plasma-glucagon-levels-using-liquid-chromatography-high-resolution-mass-spectrometry-comparison-with-commercially-available-immunoassays
#10
Atsushi Miyachi, Masaki Kobayashi, Eri Mieno, Moritaka Goto, Kenichi Furusawa, Takashi Inagaki, Tadahiro Kitamura
Accurate quantification of plasma glucagon levels in humans is necessary for understanding the physiological and pathological importance of glucagon. Although several immunoassays for glucagon are available, they provide inconsistent glucagon values owing to cross-reactivity of the antibodies with peptides other than glucagon. To overcome this limitation, we developed a novel method to measure glucagon levels by a liquid chromatography (LC)-high-resolution mass spectrometry (HRMS) assay via parallel reaction monitoring (PRM) without immunoaffinity enrichment...
August 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28799803/nutrition-inflammation-and-liver-spleen-axis
#16
Luigi Barrea, Carolina Di Somma, Giovanna Muscogiuri, Giovanni Tarantino, Gian Carlo Tenore, Francesco Orio, Annamaria Colao, Silvia Savastano
Chronic low-grade systemic inflammation represents a mechanism common to many diseases linked to atherosclerosis-related pathways. There is a growing body of evidence indicating that the combination of food quantity and quality along with genetic susceptibility are able to induce the aberrant activation of innate immune signalling, which initially contributes to chronic low-grade inflammation. Liver represents the central player to inflammatory response. Dietary/metabolic factors contribute to the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD), the main causes of liver disease in the Western world...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28799414/the-clinical-use-of-a-fixed-dose-combination-of-insulin-degludec-and-liraglutide-xultophy-100-3-6-for-the-treatment-of-type-2-diabetes
#17
Kira Harris, Kimberly Lovin Nealy
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations...
August 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28799326/glp-1-conjugated-to-rhsa-variants-with-modified-fcrn-binding-properties-impact-on-molecular-structure-and-half-life
#18
Jens Thostrup Bukrinski, Pernille Sønderby, Filipa Antunes, Birgitte Andersen, Esben Gjerloeff Wedebye Schmidt, Guenther H H J Peters, Pernille Harris
Glucagon-like peptide 1 (GLP-1) is a small incretin hormone stimulated by food intake, resulting in an amplification of the insulin response. Though interesting as a drug candidate for the treatment of type 2 diabetes mellitus, its short plasma half-life of less than 3 minutes limits its clinical use. A strategy to extend the half-life of GLP-1 utilizes the long half-life of human serum albumin (HSA) by combining the two via chemical conjugation or genetic fusion. HSA has a plasma half-life of around 21 days owing to its interaction with the neonatal Fc receptor (FcRn) expressed in endothelial cells of blood vessels, which rescues circulating HSA from lysosomal degradation...
August 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/28798686/strong-association-between-plasma-dipeptidyl-peptidase-4-activity-and-impaired-cognitive-function-in-elderly-population-with-normal-glucose-tolerance
#19
Bo Chen, Tianpeng Zheng, Linyuan Qin, Xueping Hu, Xiaoxi Zhang, Yihong Liu, Hongbo Liu, Shenghua Qin, Gang Li, Qinghua Li
Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28795473/gastrointestinal-peptides-during-chronic-gastric-electrical-stimulation-in-patients-with-intractable-vomiting
#20
Mathieu Meleine, Chloé Melchior, Philip Prinz, Alfred Penfornis, Benoît Coffin, Andreas Stengel, Philippe Ducrotté, Guillaume Gourcerol
OBJECTIVES: Gastric electrical stimulation (GES) is an alternative therapy to treat patients with intractable vomiting. A preclinical study has demonstrated the modulation of the gastrointestinal (GI) peptide ghrelin by GES but such mechanism has never been investigated in patients. The aim of this work was to assess the effect of GES on GI peptide levels in patients with intractable vomiting. MATERIALS AND METHODS: Twenty-one patients were randomized to receive either ON or OFF GES, 14 completed the study (10 ON, 4 OFF stimulation)...
August 10, 2017: Neuromodulation: Journal of the International Neuromodulation Society
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