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Diabetes AND glp-1

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https://www.readbyqxmd.com/read/29330461/comparing-olive-oil-and-c4-dietary-oil-a-prodrug-for-the-gpr119-agonist-2-oleoyl-glycerol-less-energy-intake-of-the-latter-is-needed-to-stimulate-incretin-hormone-secretion-in-overweight-subjects-with-type-2-diabetes
#1
Mette Johannsen Mandøe, Katrine Bagge Hansen, Johanne Agerlin Windeløv, Filip Krag Knop, Jens Frederik Rehfeld, Mette Marie Rosenkilde, Jens Juul Holst, Harald Severin Hansen
BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#2
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#3
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#4
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29326107/tcf7l2-genetic-variation-augments-incretin-resistance-and-influences-response-to-a-sulfonylurea-and-metformin-the-study-to-understand-the-genetics-of-the-acute-response-to-metformin-and-glipizide-in-humans-sugar-mgh
#5
Shylaja Srinivasan, Varinderpal Kaur, Bindu Chamarthi, Katherine R Littleton, Ling Chen, Alisa K Manning, Jordi Merino, Melissa K Thomas, Margo Hudson, Allison Goldfine, Jose C Florez
OBJECTIVE: The rs7903146 T allele in transcription-factor-7-like-2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. RESEARCH DESIGN AND METHODS: We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after one dose of glipizide (5 mg) on visit 1, and a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days...
January 11, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29325849/coagonist-of-glp-1-and-glucagon-decreases-liver-inflammation-and-atherosclerosis-in-dyslipidemic-condition
#6
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Dhreerendra Pandey, Hiren Patel, Ramchandra Ranvir, Shekhar Kadam, Dipam Patel, Rajesh Bahekar, Mukul Jain
Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg)...
January 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29325553/sitagliptin-improved-glucose-assimilation-in-detriment-of-fatty-acid-utilization-in-experimental-type-ii-diabetes-role-of-glp-1-isoforms-in-glut4-receptor-trafficking
#7
E Ramírez, B Picatoste, A González-Bris, M Oteo, F Cruz, A Caro-Vadillo, J Egido, J Tuñón, M A Morcillo, Ó Lorenzo
BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG)...
January 11, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29324870/incretin-responses-to-oral-glucose-and-mixed-meal-tests-and-changes-in-fasting-glucose-levels-during-7-years-of-follow-up-the-hoorn-meal-study
#8
A D M Koopman, F Rutters, S P Rauh, G Nijpels, J J Holst, J W Beulens, M Alssema, J M Dekker
We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC)...
2018: PloS One
https://www.readbyqxmd.com/read/29322485/effects-of-ipragliflozin-on-postprandial-glucose-metabolism-and-gut-peptides-in-type-2-diabetes-a-pilot-study
#9
Hiroaki Ueno, Hiroko Nakazato, Emi Ebihara, Kenji Noma, Takahisa Kawano, Kazuhiro Nagamine, Hideyuki Sakoda, Masamitsu Nakazato
INTRODUCTION: Ipragliflozin is a novel antidiabetic drug that inhibits renal tubular sodium-glucose cotransporter-2 (SGLT2). The aim of this study was to evaluate the effects of ipragliflozin on glucose, insulin, glucagon, and gastrointestinal peptide responses to a meal tolerance test, as well as to investigate the glucose-lowering mechanisms of ipragliflozin. METHODS: Nine Japanese patients with obesity and type 2 diabetes mellitus were treated with ipragliflozin (50 mg/day) for 12 weeks...
January 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29320889/the-cardiovascular-effect-of-incretin-based-therapies-among-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#10
Shanshan Wu, Andrea Cipriani, Zhirong Yang, Jun Yang, Ting Cai, Yang Xu, Xiaochi Quan, Yuan Zhang, Sanbao Chai, Feng Sun, Siyan Zhan
OBJECTIVE: To evaluate the comparative cardiovascular safety of incretin-based therapies in patients with type 2 diabetes mellitus (T2DM). METHODS: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with duration≥12 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence...
January 10, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29317623/glp-1-release-and-vagal-afferent-activation-mediate-the-beneficial-metabolic-and-chronotherapeutic-effects-of-d-allulose
#11
Yusaku Iwasaki, Mio Sendo, Katsuya Dezaki, Tohru Hira, Takehiro Sato, Masanori Nakata, Chayon Goswami, Ryohei Aoki, Takeshi Arai, Parmila Kumari, Masaki Hayakawa, Chiaki Masuda, Takashi Okada, Hiroshi Hara, Daniel J Drucker, Yuichiro Yamada, Masaaki Tokuda, Toshihiko Yada
Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316397/discovery-of-potent-and-orally-bioavailable-dihydropyrazole-gpr40-agonists
#12
Jun Shi, Zhengxiang Gu, Elizabeth Anne Jurica, Ximao Wu, Lauren E Haque, Kristin N Williams, Andres S Hernandez, Zhenqiu Hong, Qi Gao, Marta Dabros, Akin H Davulcu, Arvind Mathur, Richard A Rampulla, Arun Kumar Gupta, Ramya Jayaram, Atsu Apedo, Douglas B Moore, Heng Liu, Lori K Kunselman, Edward J Brady, Jason J Wilkes, Bradley A Zinker, Hong Cai, Yue-Zhong Shu, Qin Sun, Elizabeth A Dierks, Kimberly A Foster, Carrie Xu, Tao Wang, Reshma Panemangalore, Mary Ellen Cvijic, Chunshan Xie, Gary G Cao, Min Zhou, John Krupinski, Jean M Whaley, Jeffrey A Robl, William R Ewing, Bruce Alan Ellsworth
G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29314731/regulation-of-amino-acid-metabolism-and-alpha-cell-proliferation-by-glucagon
#13
REVIEW
Yoshitaka Hayashi, Yusuke Seino
Both glucagon and GLP-1 are produced from proglucagon through proteolytic cleavage. Blocking glucagon action increases the circulating levels of glucagon and GLP-1, reduces the blood glucose level and induces the proliferation of islet alpha cells. Glucagon blockade also suppresses hepatic amino acid catabolism and increases the serum amino acid level. In animal models defective in both glucagon and GLP-1, the blood glucose level is not reduced, indicating that GLP-1 is required for glucagon blockade to reduce the blood glucose level...
January 3, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29311617/scfas-strongly-stimulate-pyy-production-in-human-enteroendocrine-cells
#14
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310647/have-dipeptidyl-peptidase-4-inhibitors-ameliorated-the-vascular-complications-of-type-2-diabetes-in-large-scale-trials-the-potential-confounding-effect-of-stem-cell-chemokines
#15
REVIEW
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29310645/effects-of-6-month-treatment-with-the-glucagon-like-peptide-1-analogue-liraglutide-on-arterial-stiffness-left-ventricular-myocardial-deformation-and-oxidative-stress-in-subjects-with-newly-diagnosed-type-2-diabetes
#16
Vaia Lambadiari, George Pavlidis, Foteini Kousathana, Maria Varoudi, Dimitrios Vlastos, Eirini Maratou, Dimitrios Georgiou, Ioanna Andreadou, John Parissis, Helen Triantafyllidi, John Lekakis, Efstathios Iliodromitis, George Dimitriadis, Ignatios Ikonomidis
BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29302047/functional-and-association-analysis-of-an-amerindian-derived-population-specific-p-thr280met-variant-in-rbpjl-a-component-of-the-ptf1-complex
#17
Anup K Nair, Jeff R Sutherland, Michael Traurig, Paolo Piaggi, Peng Chen, Sayuko Kobes, Robert L Hanson, Clifton Bogardus, Leslie J Baier
PTF1 complex is critical for pancreatic development and maintenance of adult exocrine pancreas. As a part of our ongoing studies to identify genetic variation that contributes to type 2 diabetes (T2D) in American Indians, we analyzed variation in genes that form this complex, namely PTF1A, RBPJ, and its paralogue RBPJL. A c.839C>T (p.(Thr280Met)) variant (rs200998587:C>T, risk allele frequency = 0.03) in RBPJL, identified only in Amerindian-derived populations, associated with T2D (OR = 1.60[1...
January 4, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29301824/clinical-impact-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-uncontrolled-type-2-diabetes-and-very-high-baseline-hba1c-the-freedom-1-hbl-study
#18
Robert R Henry, Julio Rosenstock, Douglas S Denham, Prakash Prabhakar, Lise Kjems, Michelle A Baron
OBJECTIVE: ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol])...
January 4, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29295870/effect-of-liraglutide-on-atrial-natriuretic-peptide-adrenomedullin-and-copeptin-in-pcos
#19
Signe Frøssing, Malin Nylander, Caroline Kistorp, Sven O Skouby, Jens Faber
CONTEXT: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP...
January 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#20
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
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