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https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#1
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#2
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29129645/incretins-modulate-progesterone-biosynthesis-by-regulating-bone-morphogenetic-protein-activity-in-rat-granulosa-cells
#3
Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of incretins on ovarian steroidogenesis have not been clarified. In this study, we investigated the effects of incretins, including GIP and GLP-1, on ovarian steroidogenesis using rat primary granulosa cells. Treatment with incretins significantly suppressed progesterone synthesis in the presence of FSH, and the effect of GIP was more potent than that of GLP-1. In contrast, incretins had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of incretins on steroidogenesis, GIP and GLP-1 suppressed the expression of progesterogenic factors and enzymes, including StAR, P450scc, 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
November 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29128557/the-effect-of-diet-adiposity-and-weight-loss-on-the-secretion-of-incretin-hormones-in-cats
#4
K E McCool, A J Rudinsky, V J Parker, C O Herbert, C Gilor
Degree of adiposity and dietary macronutrient composition affect incretin hormone secretion in humans and mice, but little is known about their effect in cats. In this study, 7 overweight cats were fed a maintenance diet (MD) for at least 2 wk followed by a reduced calorie diet (RCD), which was lower in fat and higher in carbohydrates and fiber. Cats were fed ad libitum initially, and then, food was restricted to achieve 1%-2% loss of body weight weekly (11 wk). When lean, cats were fed MD for 2 wk. A standardized meal test (SMT) using a third diet was performed after at least 7 d on each diet, before and after weight loss (four SMT's total)...
October 20, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29101649/intestinal-incretins-and-the-regulation-of-bone-physiology
#5
Walter Ramsey, Carlos M Isales
Although originally identified as modulators of nutrient absorption, the gut hormones gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) have also been found to play an important role in the regulation of bone turnover. These "incretin" hormones promote bone anabolism by stimulating osteoblast differentiation as well as increasing osteoblast longevity. In addition, GIP and perhaps GLP-2 attenuate the activity of osteoclastic cells, leading to a net increase in bone deposition and ultimately increasing bone mass...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29099978/glucose-dependent-insulinotropic-polypeptide-gip-inhibits-bone-resorption-independently-of-insulin-and-glycemia
#6
Mikkel B Christensen, Asger Lund, Salvatore Calanna, Niklas R Jørgensen, Jens J Holst, Tina Vilsbøll, Filip K Knop
Context: The gut hormone GIP causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX). Objective: To clarify if GIP affects biomarkers involved in bone homeostasis independently of insulin release and glycemic level. Design: Randomized, double-blinded, cross-over study with 5 study days. Patients: Ten lean male C-peptide-negative patients with type 1 diabetes...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29098544/preserving-duodenal-jejunal-foregut-transit-does-not-impair-glucose-tolerance-and-diabetes-remission-following-gastric-bypass-in-type-2-diabetes-sprague-dawley-rat-model
#7
Ponnie R Dolo, Libin Yao, Chao Li, Xiaocheng Zhu, Linsen Shi, Jason Widjaja
BACKGROUND: Possible mechanisms underlying diabetes remission following Roux-en-Y gastric bypass (RYGB) include eradication of putative factor(s) with duodenal-jejunal bypass. OBJECTIVE: The objective of this study is to observe the effects of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass rat model. METHOD: In order to verify the effect of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass, 22 type 2 diabetes Sprague-Dawley rat models established through high-fat diet and low-dose streptozotocin (STZ) administered intraperitoneally were assigned to one of three groups: gastric bypass with duodenal-jejunal transit (GB-DJT n = 8), gastric bypass without duodenal-jejunal transit (RYGB n = 8), and sham (n = 6)...
November 2, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29093273/genetic-determinants-of-circulating-gip-and-glp-1-concentrations
#8
Peter Almgren, Andreas Lindqvist, Ulrika Krus, Liisa Hakaste, Emilia Ottosson-Laakso, Olof Asplund, Emily Sonestedt, Rashmi B Prasad, Esa Laurila, Marju Orho-Melander, Olle Melander, Tiinamaija Tuomi, Jens Juul Holst, Peter M Nilsson, Nils Wierup, Leif Groop, Emma Ahlqvist
The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29091932/essential-roles-of-aspartate-aminotransferase-1-and-vesicular-glutamate-transporters-in-%C3%AE-cell-glutamate-signaling-for-incretin-induced-insulin-secretion
#9
Naoya Murao, Norihide Yokoi, Kohei Honda, Guirong Han, Tomohide Hayami, Ghupurjan Gheni, Harumi Takahashi, Kohtaro Minami, Susumu Seino
Incretins (GLP-1 and GIP) potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS) that requires two critical processes: 1) generation of cytosolic glutamate through the malate-aspartate (MA) shuttle in glucose metabolism and 2) glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1), a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively), which participate in glutamate transport into secretory vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/29091882/incretin-hormones-receptor-signaling-plays-the-key-role-in-antidiabetic-potential-of-pty-2-against-stz-induced-pancreatitis
#10
Shivani Srivastava, Priya Shree, Harsh Pandey, Yamini Bhusan Tripathi
AIMS: Incretin therapy is one of the most potential approaches in the treatment of diabetes. In contrast to markedly available drugs, the herbal incretin modulators have lesser side effects with low economic cost. The main aim of this work was to analyze the potential of previously reported DPPIV inhibitor, aqueous extract of Pueraria tuberosa tubers (PTY-2) as incretin hormones receptor agonist against streptozotocin (STZ)-induced diabetes. METHODS: Chronic diabetes was induced with STZ (65mg/kg bw) in rats for 60days and grouped into diabetic control and PTY-2...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29089704/neonatal-gastrointestinal-perforations-the-10-year-experience-of-a-reference-hospital
#11
Mehmet Saraç, Ünal Bakal, Mustafa Aydın, Tugay Tartar, Aysen Orman, Erdal Taşkın, Şenay Canpolat, Ahmet Kazez
The aim of this study was to present our experiences with, as well as the factors that affect, the treatment and outcome of patients with neonatal gastrointestinal perforations (GIPs). Thirty-eight newborn cases that were operated on for GIP in our hospital's tertiary newborn intensive care unit between January 2005 and December 2015 were retrospectively evaluated. The patients were divided into the two following groups: group 1, perforations related to necrotizing enterocolitis (NEC), and group 2, non-NEC perforations...
October 2017: Indian Journal of Surgery
https://www.readbyqxmd.com/read/29074486/metabolic-markers-of-protein-maldigestion-after-a-15-n-test-meal-in-minipigs-with-pancreatic-exocrine-insufficiency
#12
Florence Mary, Anne Moesseler, Nadezda Khodorova, Angélique Foucault-Simonin, Robert Benamouzig, Daniel Tomé, Peter Colin Gregory, Claire Gaudichon
The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a (15)N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four non-operated animals as a control. All animals were equipped with an ileo-caecal re-entrant cannula. Minipigs were given a test meal containing (15)N casein. The PEI animals repeated the test 3 times, in the absence of any pancreatic enzymes, or after pancreatic substitution at 2 levels (A or B: 7500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U)...
October 26, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29056448/evolution-of-the-glucagon-like-system-across-fish
#13
João C R Cardoso, Rute C Félix, Carina Costa, Pedro F S Palma, Adelino V M Canário, Deborah M Power
In fishes, including the jawless lampreys, the most ancient lineage of extant vertebrates, plasma glucose levels are highly variable and regulation is more relaxed than in mammals. The regulation of glucose and lipid in fishes in common with mammals involves members of the glucagon (GCG)-like family of gastrointestinal peptides. In mammals, four peptides GCG, glucagon-like peptide 1 and 2 (GLP1 and GLP2) and glucose-dependent insulinotropic peptide (GIP) that activate four specific receptors exist. However, in lamprey and other fishes the glucagon-like family evolved differently and they retained additional gene family members (glucagon-related peptide, gcrp and its receptor, gcrpr) that are absent from mammals...
October 19, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29054256/drug-target-interaction-prediction-a-bayesian-ranking-approach
#14
Ladislav Peska, Krisztian Buza, Júlia Koller
BACKGROUND AND OBJECTIVE: In silico prediction of drug-target interactions (DTI) could provide valuable information and speed-up the process of drug repositioning - finding novel usage for existing drugs. In our work, we focus on machine learning algorithms supporting drug-centric repositioning approach, which aims to find novel usage for existing or abandoned drugs. We aim at proposing a per-drug ranking-based method, which reflects the needs of drug-centric repositioning research better than conventional drug-target prediction approaches...
December 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29050859/neuroprotective-effects-of-a-triple-glp-1-gip-glucagon-receptor-agonist-in-the-app-ps1-transgenic-mouse-model-of-alzheimer-s-disease
#15
Jingjing Tai, Weizhen Liu, Yanwei Li, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Previous studies have shown that the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) that have anti-diabetic properties show very promising effects in animal models of AD. Glucagon (Gcg) is a hormone and growth-factor, and the Gcg receptor is expressed in the brain. Here we test the effects of a triple receptor agonist (TA), which activates GIP-1, GIP and glucagon receptors at the same time...
October 16, 2017: Brain Research
https://www.readbyqxmd.com/read/29044772/rd-lawrence-lecture-2017-incretins-the-intelligent-hormones-in-diabetes
#16
V A Gault
The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have attracted considerable scientific and clinical interest due largely to their insulin-releasing and glucose-lowering properties. Indeed, GLP-1-based therapies are now key treatment options for many people with diabetes worldwide. In contrast, GIP-based agents have yet to reach the clinic based primarily on the impaired insulinotropic action of GIP observed in people with diabetes. Nevertheless, GIP is a key physiological regulator of insulin secretion and stable forms of GIP show much promise in rodent models to alleviate diabetes-obesity...
October 16, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29041949/incretins-in-patients-with-rheumatoid-arthritis
#17
Beatriz Tejera-Segura, Raquel López-Mejías, María Jesús Domínguez-Luis, Antonia M de Vera-González, Alejandra González-Delgado, Begoña Ubilla, José M Olmos, José L Hernández, Miguel A González-Gay, Iván Ferraz-Amaro
BACKGROUND: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. METHODS: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects...
October 17, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29034596/regulation-of-glucagon-like-peptide-1-sensitivity-by-gut-microbiota-dysbiosis
#18
Shunsuke Yamane, Nobuya Inagaki
Gut hormonal substances released in response to nutrients include incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Together, incretins are responsible for 50%-60% of postprandial insulin secretion. Oral glucose administration leads to greater insulin release from pancreatic islets than intravenous glucose loading that yields equivalent blood glucose levels; this phenomenon is called the incretin effect. This article is protected by copyright. All rights reserved.
October 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29031770/effects-of-three-major-amino-acids-found-in-japanese-broth-on-glucose-metabolism-and-gastric-emptying
#19
Fumika Mano, Kaori Ikeda, Erina Joo, Shunsuke Yamane, Norio Harada, Nobuya Inagaki
OBJECTIVES: To our knowledge, the effect of the broth of dried kelp and dried bonito, dashi, on glucose metabolism and digestion has rarely been studied. Based on the component analysis of three actual broths served in traditional restaurants, a chemically synthesized broth with three free amino acids (histidine, glutamate, aspartate) and salt was prepared to investigate their effect on glucose metabolism, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) secretion, and digestion...
August 10, 2017: Nutrition
https://www.readbyqxmd.com/read/29031728/single-cell-rna-sequencing-reveals-a-distinct-population-of-proglucagon-expressing-cells-specific-to-the-mouse-upper-small-intestine
#20
Leslie L Glass, Fernando J Calero-Nieto, Wajid Jawaid, Pierre Larraufie, Richard G Kay, Berthold Göttgens, Frank Reimann, Fiona M Gribble
OBJECTIVES: To identify sub-populations of intestinal preproglucagon-expressing (PPG) cells producing Glucagon-like Peptide-1, and their associated expression profiles of sensory receptors, thereby enabling the discovery of therapeutic strategies that target these cell populations for the treatment of diabetes and obesity. METHODS: We performed single cell RNA sequencing of PPG-cells purified by flow cytometry from the upper small intestine of 3 GLU-Venus mice. Cells from 2 mice were sequenced at low depth, and from the third mouse at high depth...
October 2017: Molecular Metabolism
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