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Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Pengyu Yang, Huafei Zou, Candy Lee, Avinash Muppidi, Elizabeth Chao, Qiangwei Fu, Xiaozhou Luo, Danling Wang, Peter G Schultz, Weijun Shen
Glucagon-like peptide 2 (GLP-2) is a hormone that has been shown to stimulate intestinal growth and attenuate intes-tinal inflammation. Despite being efficacious in a variety of animal models of disease, its therapeutic potential is ham-pered by the short half-life in vivo. We now describe a highly potent, stapled long-acting GLP-2 analog, Peptide 10, that has a more than 10-fold longer half-life than teduglutide and improved intestinotrophic and anti-inflammatory effects in mouse models of DSS-induced colitis...
March 12, 2018: Journal of Medicinal Chemistry
David L Sigalet, Viona Lam, Mary Brindle, Dana Boctor, Laurie Wallace, Elaine de Heuval, Bollette Hartmann, Jens J Holst
PURPOSE: This study investigates the relationship between the enteric hormone glucagon-like peptide 2 (GLP-2) production, sensitivity, and intestinal adaptation in infants following resection or repair of gastroschisis. METHODS: With IRB approval (UCalgary #10656), consent was obtained from families of infants undergoing surgery for prospective monitoring of nutritional status, GLP-2 levels, and where possible, tissue sampling. RESULTS: Infants who adapted and weaned from parenteral nutrition (PN) had increased GLP-2 (86±32) n=24 vs...
February 7, 2018: Journal of Pediatric Surgery
David M Irwin, Svetlana Mojsov
The teleost fish-specific genome duplication gave rise to a great number of species inhabiting diverse environments with different access to nutrients and life histories. This event produced duplicated gcg genes, gcga and gcgb, for proglucagon-derived peptides, glucagon and GLP-1 and duplicated gcgr receptor genes, gcgra and gcgrb, which play key roles connecting the consumption of nutrients with glucose metabolism. We conducted a systematic survey of the genomes from 28 species of fish (24 bony (Superclass Osteichthyes), 1 lobe-finned (Class Sarcoperygii), 1 cartilaginous (Superclass Chondrichthyes), and 2 jawless (Superclass Agnatha)) and find that almost all surveyed ray-finned fish contain gcga and gcgb genes with different coding potential and duplicated gcgr genes, gcgra and gcgrb that form two separate clades in the phylogenetic tree consistent with the accepted species phylogeny...
March 3, 2018: General and Comparative Endocrinology
Kwai Lam, Lauren Schwartz, Jennifer Batisti, Kishore R Iyer
BACKGROUND: Teduglutide is a glucagon-like peptide 2 (GLP-2) analog that has been approved for the treatment of adult short bowel syndrome (SBS)-associated intestinal failure (IF; SBS-IF). Teduglutide increases villus height and crypt depth in the small bowel mucosa, promoting nutrition absorption and enteral independence from parenteral nutrition (PN). We aim to report our single-center experience with teduglutide in adult patients with SBS to provide real-world context to its use. METHOD: We conducted a retrospective analysis on patients managed within our tertiary-level intestinal rehabilitation program to identify patients with SBS-IF treated with teduglutide from 2009-2015...
January 2018: JPEN. Journal of Parenteral and Enteral Nutrition
M A de Laat, D M Fitzgerald, M N Sillence, R J Spence
BACKGROUND: Equine insulin dysregulation (ID) is a common and poorly understood disorder that increases the risk of laminitis. Recent data show that the condition may be associated with alteration of the enteroinsular axis and enhanced glucose bioavailability. Upregulation of glucagon-like peptide-2 (GLP-2), an intestinotrophic peptide, leads to enhanced nutrient uptake and metabolic dysfunction in other species. OBJECTIVES: The study aimed to 1) determine whether GLP-2 is differentially expressed in insulin-dysregulated ponies, compared to healthy ponies, and 2) confirm intestinal expression of the GLP-2 receptor in horses (eGLP-2R)...
March 4, 2018: Equine Veterinary Journal
M Desjardins-Morrissette, J K van Niekerk, D Haines, T Sugino, M Oba, M A Steele
The objective of this study was to determine if feeding colostrum to newborn calves through an esophageal tube, compared with a nipple bottle, would delay abomasal emptying, which would in turn decrease passive transfer of IgG and plasma glucose, insulin, and glucagon-like peptide (GLP) 1 and GLP-2 concentrations. Twenty newborn Holstein bull calves were fed 3 L of colostrum replacer (200 g of IgG) through either an esophageal tube or nipple bottle at 2 h after birth followed by feeding pooled whole milk every 12 h after birth...
February 14, 2018: Journal of Dairy Science
Najeeha Talat Iqbal, Kamran Sadiq, Sana Syed, Tauseefullah Akhund, Fayyaz Umrani, Sheraz Ahmed, Mohammad Yawar Yakoob, Najeeb Rahman, Shahida Qureshi, Wenjun Xin, Jennie Z Ma, Molly Hughes, Syed Asad Ali
Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkers associated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months...
February 14, 2018: Scientific Reports
Daming Sun, Hongwei Li, Shengyong Mao, Weiyun Zhu, Junhua Liu
The objective of this study was to investigate the effects of different source of starch in starter feed on small intestinal growth and endogenous glucagon-like peptide 2 (GLP-2) secretion in pre-weaned lambs. Twenty-four 10-day-old lambs were divided into three groups that were treated with different iso-starch diets containing purified cassava starch (CS, n = 8), maize starch (MS, n = 8) and pea starch (PS, n = 8). At 56 days old, there was no significant difference in final body weight (BW) of lambs among the three groups...
February 8, 2018: Journal of Animal Science
Erin E Mulvihill
PURPOSE OF REVIEW: The intestine is highly efficient at absorbing and packaging dietary lipids onto the structural protein apoB48 for distribution throughout the body. Here, we summarize recent advances into understanding the physiological and pharmacological actions of the proglucagon-derived peptides: glucagon like peptide 1 (GLP-1) and glucagon like peptide 2 (GLP-2) on intestinal lipoprotein secretion. RECENT FINDINGS: Several recent studies have elucidated mechanisms underlying the paradoxical effects of GLP-1 and GLP-2 on intestinal production of triglyceride-rich lipoproteins (TRLs)...
February 9, 2018: Current Opinion in Lipidology
Qiucheng Lei, Jingcheng Bi, Huanwei Chen, Feng Tian, Xuejin Gao, Ning Li, Xinying Wang
Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet: chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 μg bid per mouse, n = 10) provided for 5 days...
January 2018: Nutrition Research
Qian Zhang, Mengge Liu, Shiyu Li, Zhenrui Xu, Jiajia Wang, Yuzhe Wang, Zhengbin Fei, Wenhua Huang, Hanxiao Sun
Bifidobacterium has been developed for the oral delivery of peptides and has the added beneficial effect on our bodies through its probiotic properties. Here, we utilize Bifidobacterium as a delivery system to orally deliver Glucagon like peptide-2 (GLP-2). We constructed vector derived from pET-31b(+) to construct a Bifidobacterium longum expressing GLP-2. We then determined the bioactivity of recombinant Bifidobacterium in Caco-2 cells. Finally, we quantified newly synthesized ApoB48 and chylomicron production in mice infused with exogenous GLP-2 or Bifidobacterium expressing GLP-2...
January 9, 2018: Journal of Microbiological Methods
Linea Landgrebe Ring, Nikolaj Nerup, Palle Bekker Jeppesen, Lars Bo Svendsen, Michael Patrick Achiam
Glucagon like peptide-2 is synthesized from enteroendocrine L cells primarily located in the ileum and large intestine. GLP-2 stimulates crypt cell proliferation, increases intestinal blood flow, enhances gut barrier function, induces mucosal healing, and exerts an anti-apoptotic effect. Due to these effects GLP-2 is used in the treatment of short bowel syndrome (SBS). Areas covered: The aim of this systematic review was to provide information on the potential risk of intestinal neoplasia in patients receiving treatment with GLP-2...
March 2018: Expert Review of Gastroenterology & Hepatology
Daniel J Drucker, Joel F Habener, Jens Juul Holst
The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies...
December 1, 2017: Journal of Clinical Investigation
Md Abdul Halim, Marie Degerblad, Magnus Sundbom, Urban Karlbom, Jens Juul Holst, Dominic-Luc Webb, Per M Hellström
Context: Glucagon-like peptide-1 (GLP-1) secretion from l-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 inhibit human postprandial motility and determine mechanism of action of GLP-1 and analog ROSE-010 action. Design: Single-blind parallel study. Setting: University hospital laboratory. Participants: Healthy volunteers investigated with antroduodenal manometry...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
Eleonora Cremonini, Ziwei Wang, Ahmed Bettaieb, Ana M Adamo, Elena Daveri, David A Mills, Karen M Kalanetra, Fawaz G Haj, Sidika Karakas, Patricia I Oteiza
Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance...
April 2018: Redox Biology
Rachele Garella, Eglantina Idrizaj, Chiara Traini, Roberta Squecco, Maria Giuliana Vannucchi, Maria Caterina Baccari
AIM: To investigate whether glucagon-like peptide-2 (GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available. METHODS: For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation (EFS) was applied via two platinum wire rings through which the preparation was threaded...
October 28, 2017: World Journal of Gastroenterology: WJG
N Yacoubi, L Saulnier, E Bonnin, E Devillard, V Eeckhaut, L Rhayat, R Ducatelle, F Van Immerseel
Carbohydrate-degrading multi-enzyme preparations (MEP) are used to improve broiler performances. Their mode of action is complex and not fully understood. In this study, we compared the effect of water-soluble fractions isolated at the pilot scale from wheat grain incubated with (WE) and without (WC) MEP. The fractions were incorporated in a wheat-based diet (0.1% w/w) to feed Ross PM3 broilers and compared with a non-supplemented control group (NC). The body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) until d 14 were determined...
November 10, 2017: Poultry Science
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
A Pal, D B Rhoads, A Tavakkoli
Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion...
February 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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