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https://www.readbyqxmd.com/read/29352262/microbial-regulation-of-the-l-cell-transcriptome
#1
Tulika Arora, Rozita Akrami, Ramona Pais, Linda Bergqvist, Bengt R Johansson, Thue W Schwartz, Frank Reimann, Fiona M Gribble, Fredrik Bäckhed
L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351476/human-endoc-%C3%AE-h1-%C3%AE-cells-form-pseudoislets-with-improved-glucose-sensitivity-and-enhanced-glp-1-signaling-in-the-presence-of-islet-derived-endothelial-cells
#2
Michael G Spelios, Lauren A Afinowicz, Regine C Tipon, Eitan M Akirav
Three-dimensional (3D) pseudoislets (PIs) can be used for the study of insulin-producing β-cells in free-floating islet-like structures similar to that of primary islets. Previously, we demonstrated the ability of islet-derived endothelial cells (iECs) to induce PIs using murine insulinomas, where PI formation enhanced insulin production and glucose responsiveness. In this report, we examined the ability of iECs to spontaneously induce the formation of free-floating 3D PIs using the EndoC-βH1 human β-cell line murine MS1 iEC line...
January 16, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351421/increased-insulin-clearance-in-mice-with-double-deletion-of-glucagon-like-peptide-1-and-glucose-dependent-insulinotropic-polypeptide-receptors
#3
Andrea Tura, Roberto Bizzotto, Yuichiro Yamada, Yutaka Seino, Giovanni Pacini, Bo Ahren
To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n=31) and wild-type (WT) C57BL6J mice (n=45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 minutes and assayed for glucose, insulin and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection...
January 3, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351394/bile-acid-profiles-within-the-enterohepatic-circulation-in-a-diabetic-rat-model-after-bariatric-surgeries
#4
Meng Wei, Yi Shao, Qiao-Ran Liu, Qun-Zheng Wu, Xiang Zhang, Ming-Wei Zhong, Shao-Zhuang Liu, Guang-Yong Zhang, San-Yuan Hu
Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries, although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects...
December 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29350569/practice-pearl-liraglutide-and-cardiovascular-and-renal-events-in-type-2-diabetes
#5
Robert Guthrie
Review of: Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322. Mann J, Orsted D, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848. This comprehensive research project, LEADER, led to two reports, one focusing on the effect of liraglutide on cardiovascular events, and the second one reporting on the renal effects on the same study population. The study group included 9340 patients with type 2 diabetes...
January 19, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29348573/exendin-4-encapsulated-dissolving-microneedle-arrays-for-efficient-treatment-of-type-2-diabetes
#6
Shayan Fakhraei Lahiji, Yoojung Jang, Inyoung Huh, Huisuk Yang, Mingyu Jang, Hyungil Jung
Dissolving microneedles (DMNs) are microscopic needles capable of delivering encapsulated compounds and releasing them into the skin in a minimally invasive manner. Most studies indicate that encapsulating therapeutics in DMNs is an efficacious approach; however, the importance of evaluating the activity of encapsulated compounds, during the fabrication process, has not been examined in detail. Conducting an analysis of thermal, chemical, and physical stress factors, including temperature, pH, and the interaction of the polymer and therapeutics mixture during preparation, is essential for retaining the activity of encapsulated therapeutics during and after fabrication...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345505/the-pharmacological-management-of-metabolic-syndrome
#7
Julie Rask Larsen, Lorena Dima, Christoph U Correll, Peter Manu
Introduction The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice...
January 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29344656/liraglutide-suppresses-proliferation-and-induces-adipogenic-differentiation-of-3t3-l1-cells-via-the-hippo-yap-signaling-pathway
#8
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344336/treating-nonalcoholic-fatty-liver-disease-in-patients-with-type-2-diabetes-mellitus-a-review-of-efficacy-and-safety
#9
REVIEW
Elizabeth P Mills, K Paige D Brown, Jennifer D Smith, Phillip W Vang, Katie Trotta
Objective: To review current literature for the efficacy and safety of treatment for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to June 2017 was conducted using the search terms nonalcoholic fatty liver disease, diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin...
January 2018: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#10
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29341824/intestinal-lymph-as-a-readout-of-meal-induced-glp-1-release-in-an-unrestrained-rat-model
#11
Nino Jejelava, Sharon Kaufman, Jean-Philippe Krieger, Marcella Martins Terra, Wolfgang Langhans, Myrtha Arnold
Intestinal lymph supposedly provides a readout for the secretion of intestinal peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of glucagon-like peptide (GLP-1), insulin, and metabolites (Glucose, triglycerides [TG]) evolve after isocaloric high and low fat diet (HFD, LFD) meals, and how they compare to hepatic portal vein (HPV) plasma levels. Moreover, we examined the effects of intraperitoneally (IP) administered GLP-1 (1 or 10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels were higher in MLD lymph than in HPV plasma...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#12
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29341370/real-world-clinical-outcomes-and-predictors-of-glycaemic-and-weight-response-to-exenatide-once-weekly-in-patients-with-type-2-diabetes-the-cibeles-project
#13
Juan José Gorgojo-Martínez, Manuel Angel Gargallo-Fernández, Miguel Brito-Sanfiel, Arturo Lisbona-Catalán
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists...
January 17, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29339245/systematic-review-and-evaluation-of-aspartame-carcinogenicity-bioassays-using-quality-criteria
#14
REVIEW
Lois Haighton, Ashley Roberts, Brandon Walters, Barry Lynch
The current review assessed cancer studies of aspartame based on a quality appraisal using the Klimisch grading system. Nine studies having complete histopathology were included: three 2-year studies by Searle; three transgenic mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A tenth study limited to brain tumors was not rated. None were determined as Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP standards but their methodology was comparable; transgenic mouse models are not validated, but are accepted as supporting data...
January 12, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29339031/resolution-of-type-2-diabetes-after-sleeve-gastrectomy-a-2-step-hypothesis
#15
Federico Sista, Valentina Abruzzese, Marco Clementi, Stefano Guadagni, Laura Montana, Sergio Carandina
BACKGROUND: Weight loss (WL) and altered gut hormonal levels are involved in glucose homeostasis after laparoscopic sleeve gastrectomy (LSG). OBJECTIVES: The aim of this study was to evaluate the time-related effects of WL, ghrelin, and glucacon-like peptide-1 (GLP-1) plasma concentrations on type 2 diabetes resolution after LSG. SETTING: University hospital, Italy. METHODS: Ninety-one patients who underwent LSG were investigated...
December 14, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/29337226/glp-1-signaling-and-alcohol-mediated-behaviors-preclinical-and-clinical-evidence
#16
REVIEW
Elisabet Jerlhag
Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration...
January 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29335890/effectiveness-of-sodium-glucose-cotransporter-2-inhibitor-as-an-add-on-drug-to-glp-1-receptor-agonists-for-glycemic-control-of-a-patient-with-prader-willi-syndrome-a-case-report
#17
Yukio Horikawa, Mayumi Enya, Makie Komagata, Ken-Ichi Hashimoto, Masayo Kagami, Maki Fukami, Jun Takeda
INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents...
January 15, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29335487/increased-expression-of-glp-1r-in-proliferating-islets-of-men1-mice-is-detectable-by-68ga-ga-do3a-vs-cys40-exendin-4-pet
#18
Azita Monazzam, Joey Lau, Irina Velikyan, Su-Chen Li, Masoud Razmara, Ulrika Rosenström, Olof Eriksson, Britt Skogseid
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334697/sepsis-induced-activation-of-endogenous-glp-1-system-is-enhanced-in-type-2-diabetes
#19
Sivan H Perl, Olga Bloch, Dana Zelnic-Yuval, Itamar Love, Lior Mendel-Cohen, Hadar Flor, Micha J Rapoport
BACKGROUND: High levels of circulating GLP-1 are associated with severity of sepsis in critically ill non-diabetic patients. Whether type 2 diabetes (T2D) patients display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes related metabolic parameters is not known. METHODS: Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2-4 days in 37 sepsis patients with (n=13) and without T2D (n=24) and compared to normal healthy controls (n=25)...
January 15, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#20
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
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