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https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#1
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#2
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28713911/glucagon-like-peptide-1-analogue-liraglutide-ameliorates-atherogenesis-via-inhibiting-advanced-glycation-end-product-induced-receptor-for-advanced-glycosylation-end-product-expression-in-apolipoprotein-e-deficient-mice
#3
Peicheng Li, Zhaosheng Tang, Lin Wang, Bo Feng
Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10 weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713266/significance-of-microbiota-in-obesity-and-metabolic-diseases-and-the-modulatory-potential-by-medicinal-plant-and-food-ingredients
#4
REVIEW
Hoda M Eid, Michelle L Wright, N V Anil Kumar, Abdel Qawasmeh, Sherif T S Hassan, Andrei Mocan, Seyed M Nabavi, Luca Rastrelli, Atanas G Atanasov, Pierre S Haddad
Metabolic syndrome is a cluster of three or more metabolic disorders including insulin resistance, obesity, and hyperlipidemia. Obesity has become the epidemic of the twenty-first century with more than 1.6 billion overweight adults. Due to the strong connection between obesity and type 2 diabetes, obesity has received wide attention with subsequent coining of the term "diabesity." Recent studies have identified unique contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712893/the-glucagon-like-peptide-1-analogue-liraglutide-promotes-autophagy-through-the-modulation-of-5-amp-activated-protein-kinase-in-ins-1-%C3%AE-cells-under-high-glucose-conditions
#5
Xinyu Miao, Zhaoyan Gu, Yu Liu, Mengmeng Jin, Yanhui Lu, Yanping Gong, Lin Li, Chunlin Li
Glucagon-like peptide-1 (GLP-1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic β-cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic β-cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP-1-induced protection of pancreatic β-cells exposed to high glucose...
July 13, 2017: Peptides
https://www.readbyqxmd.com/read/28711731/insulin-chains-as-efficient-fusion-tags-for-prokaryotic-expression-of-short-peptides
#6
Ligang Deng, Xiaoying Xue, Cangjie Shen, Xiaohan Song, Chunyang Wang, Nan Wang
Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting...
July 12, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#7
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#8
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28707223/inhibition-of-exendin-4-induced-steatosis-by-protein-kinase-a-in-cultured-hepg2-human-hepatoma-cells
#9
Alice Y Chen-Liaw, Gabrielle Hammel, George Gomez
Nonalcoholic fatty liver is characterized by the abnormal accumulation of triglycerides within hepatocytes, resulting in a steatotic liver. Glucagon-like peptide 1 and its analog exendin-4 can ameliorate certain aspects of this syndrome by inducing weight loss and reducing hepatic triglyceride accumulation, but it is unclear whether these effects result from the effects of glucagon-like peptide 1 on the pancreas, or from direct action on the liver. This study investigated the direct action and putative cellular mechanism of exendin-4 on steatotic hepatocytes in culture...
July 13, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28705805/validation-and-characterization-of-a-novel-method-for-selective-vagal-deafferentation-of-the-gut
#10
Charlene Diepenbroek, Danielle Quinn, Ricky Stephens, Benjamin Zollinger, Seth Anderson, Annabelle Pan, Guillaume de Lartigue
There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the GI hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a sub-population of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine, but not the colon, while leaving vagal efferent neurons intact...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28704555/a-system-model-of-the-effects-of-exercise-on-plasma-interleukin-6-dynamics-in-healthy-individuals-role-of-skeletal-muscle-and-adipose-tissue
#11
Micaela Morettini, Maria Concetta Palumbo, Massimo Sacchetti, Filippo Castiglione, Claudia Mazzà
Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution...
2017: PloS One
https://www.readbyqxmd.com/read/28704315/appetite-regulations-after-sprint-exercise-under-hypoxic-condition-in-female-athletes
#12
Chihiro Kojima, Nobukazu Kasai, Aya Ishibashi, Yukako Murakami, Kumiko Ebi, Kazushige Goto
The present study determined changes in appetite-regulating hormones and energy intake after high-intensity interval exercise (HIIT) under hypoxic conditions in trained female athletes. Fifteen female athletes completed three trials on different days of either HIIT under hypoxic conditions (HYP), HIIT under normoxic conditions (NOR), or rest in normoxia (CON). Exercise trials consisted of two successive sets of eight repeated bouts of a 6-s maximal sprint separated by a 30-s rest. Blood samples were obtained to measure plasma acylated ghrelin, glucagon-like peptide-1 (GLP-1), and metabolite concentrations...
July 12, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28702330/neonatal-glp1r-activation-limits-adult-adiposity-by-durably-altering-hypothalamic-architecture
#13
Andrea V Rozo, Daniella A Babu, PoMan A Suen, David N Groff, Randy J Seeley, Rebecca A Simmons, Patrick Seale, Rexford S Ahima, Doris A Stoffers
OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28702324/the-endogenous-preproglucagon-system-is-not-essential-for-gut-growth-homeostasis-in-mice
#14
Pernille Wismann, Pernille Barkholt, Thomas Secher, Niels Vrang, Henrik B Hansen, Palle Bekker Jeppesen, Laurie L Baggio, Jacqueline A Koehler, Daniel J Drucker, Darleen A Sandoval, Jacob Jelsing
OBJECTIVE: The prevalence of obesity and related co-morbidities is reaching pandemic proportions. Today, the most effective obesity treatments are glucagon-like peptide 1 (GLP-1) analogs and bariatric surgery. Interestingly, both intervention paradigms have been associated with adaptive growth responses in the gut; however, intestinotrophic mechanisms associated with or secondary to medical or surgical obesity therapies are poorly understood. Therefore, the objective of this study was to assess the local basal endogenous and pharmacological intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28701318/%C3%A2-liraglutide-for-weight-management
#15
(no author information available yet)
Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world, largely as a result of adverse effects.(1) For several years, orlistat has been the only drug licensed in the UK for weight management.(2) In January 2017, a new presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide (▾Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults. Here, we review the evidence for its efficacy and safety and consider its place in managing people who are overweight or obese...
July 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28701300/duodenal-and-ileal-glucose-infusions-differentially-alter-gastrointestinal-peptides-appetite-response-and-food-intake-a-tube-feeding-study
#16
Sally D Poppitt, Hyun Sang Shin, Anne-Thea McGill, Stephanie C Budgett, Kim Lo, Malcolm Pahl, Janice Duxfield, Mark Lane, John R Ingram
Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies.Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides.Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration...
July 12, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28700581/corrigendum-crystal-structure-of-the-glp-1-receptor-bound-to-a-peptide-agonist
#17
Ali Jazayeri, Mathieu Rappas, Alastair J H Brown, James Kean, James C Errey, Nathan J Robertson, Cédric Fiez-Vandal, Stephen P Andrews, Miles Congreve, Andrea Bortolato, Jonathan S Mason, Asma H Baig, Iryna Teobald, Andrew S Doré, Malcolm Weir, Robert M Cooke, Fiona H Marshall
This corrects the article DOI: 10.1038/nature22800.
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28699892/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#18
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-anti-obesity-effects-in-diet-induced-obese-mice
#19
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
Glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans in addition to their potent anti-diabetic effects. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their anti-obesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog, exenatide, for the development of promising new anti-obesity drugs...
July 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#20
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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