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Gastrin AND Incretin

Ines Bilic-Curcic, Maja C Berkovic
BACKGROUND AND OBJECTIVES: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from nonresponders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP- 1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying...
November 16, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
Olga Kruszelnicka, Marcin Kuźma, Iwona Z Pena, Ian B Perera, Bernadeta Chyrchel, Ewa Wieczorek-Surdacka, Andrzej Surdacki
Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates β-cell neogenesis and enhances insulin release, exerting an incretin-like effect. Our aim was to assess, if PPI usage is associated with altered glycaemia in patients with CV disease. Methods: We retrospectively analyzed medical records of 102 subjects (80 with ischemic heart disease) who underwent a routine oral glucose tolerance test while hospitalized in a cardiology department...
2017: International Journal of Medical Sciences
Ulrich Rohde
Bariatric surgery (e.g. Roux-en-Y gastric bypass (RYGB)) has proven the most effective way of achieving sustainable weight losses and remission of type 2 diabetes (T2D). Studies indicate that the effectiveness of RYGB is mediated by an altered gastrointestinal tract anatomy, which in particular favours release of the gut incretin hormone glucagon-like peptide-1 (GLP-1). The EndoBarrier gastrointestinal liner or duodenal-jejunal bypass sleeve (DJBS) is an endoscopic deployable minimally invasive and fully reversible technique designed to mimic the bypass component of the RYGB...
November 2016: Danish Medical Journal
G S M Paula, L L Souza, N O S Bressane, R Maravalhas, M Wilieman, T Bento-Bernardes, K R Silva, L S Mendonca, K J Oliveira, C C Pazos-Moura
Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48...
December 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
P A Senior, A Koh, J Yau, S Imes, P Dinyari, A J Malcolm, P Light, A M J Shapiro
AIMS: Resuming insulin use due to waning function is common after islet transplantation. Animal studies suggest that gastrointestinal hormones, including gastrin and incretins may increase β-cell mass. We tested the hypothesis that pantoprazole plus sitagliptin, would restore insulin independence in islet transplant recipients with early graft insufficiency and determined whether this would persist after a 3-month washout. METHODS: Single-centre, uncontrolled, open label study of sitagliptin 100 mg daily plus pantoprazole 40 mg twice daily for 6 months...
February 2017: Diabetic Medicine: a Journal of the British Diabetic Association
Juris J Meier, Michael A Nauck
The development of incretin-based therapies (glucagon-like peptide 1 [GLP-1] receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) has changed the landscape of type 2 diabetes management over the past decade. Current developments include longer-acting GLP-1 receptor agonists, fixed-ratio combinations of GLP-1 analogues and basal insulin, as well as implantable osmotic minipumps for long-term delivery of GLP-1 receptor agonists. In longer terms, oral or inhaled GLP-1 analogues may become a reality...
August 2015: Diabetologia
Ilaria Barchetta, Chiara Guglielmi, Laura Bertoccini, Damiano Calella, Silvia Manfrini, Chiara Secchi, Paolo Pozzilli, Maria Gisella Cavallo
AIMS: Experimental data demonstrated that gastrin has incretin-like stimulating actions on β-cells, resulting in a promotion of glucose-induced insulin secretion. As proton pump inhibitors (PPIs) consistently increase plasma gastrin levels, a possible effect of this treatment on glucose-insulin homeostasis may be hypothesized. Therefore, the aim of this study was to evaluate the effect of chronic PPIs treatment on glycemic control in patients affected by type 2 diabetes. METHODS: This is an observational, retrospective study...
October 2015: Acta Diabetologica
Natalie A Terry, Erik R Walp, Randall A Lee, Klaus H Kaestner, Catherine Lee May
Enteroendocrine cells secrete over a dozen different hormones responsible for coordinating digestion, absorption, metabolism, and gut motility. Loss of enteroendocrine cells is a known cause of severe congenital diarrhea. Furthermore, enteroendocrine cells regulate glucose metabolism, with the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) playing critical roles in stimulating insulin release by pancreatic β-cells. Islet1 (Isl1) is a LIM-homeodomain transcription factor expressed specifically in an array of intestinal endocrine cells, including incretin-expressing cells...
November 15, 2014: American Journal of Physiology. Gastrointestinal and Liver Physiology
David P Sonne, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
OBJECTIVE: Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1(GCG)) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility...
October 2014: European Journal of Endocrinology
Motoyuki Tamaki, Yoshio Fujitani, Toyoyoshi Uchida, Takahisa Hirose, Ryuzo Kawamori, Hirotaka Watada
UNLABELLED: Aim/Introduction:  Preservation of β-cell mass is crucial for maintaining long-term glucose homeostasis. Therapies based on incretin and its mimetics are expected to achieve this goal through various biological functions, particularly the restoration of β-cell mass. Here we tested the effects of gastrin and exendin-4 in type 2 diabetic animals. MATERIALS AND METHODS:   The effects of exendin-4 and gastrin on β-cell function and mass were examined in 8-week-old db/db mice...
October 19, 2010: Journal of Diabetes Investigation
F Inci, M Atmaca, M Ozturk, S Yildiz, R Koceroglu, R Sekeroglu, S H Ipekci, L Kebapcilar
BACKGROUND: Proton pump inhibitors induce hypergastrinemia by suppressing gastric acidity. Gastrin has incretin-like stimulating actions on beta cells. Proton pump inhibitors have been shown to decrease glycosylated hemoglobin. AIM: We aimed to observe changes in beta cell function in diabetic and non-diabetic subjects given pantoprazole for an acid-related ailment. METHODS: Seventy-nine male patients (38 non-diabetic and 41 type-2 diabetic receiving only metformin therapy) were followed for 12 weeks after pantoprazole 40 mg/day was given...
May 2014: Journal of Endocrinological Investigation
Rod Dimaline, Andrea Varro
The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as plasminogen activator inhibitors and matrix metalloproteinases that have important actions on extracellular matrix remodelling. These actions are, at least in part, effected by paracrine signalling pathways and make important contributions to maintaining functional integrity of the gastric epithelium...
July 15, 2014: Journal of Physiology
David P Sonne, Kristine J Hare, Pernille Martens, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ)...
February 15, 2013: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jean Claude Reubi
A precise definition of the tumor tissue targets to be selected for in vivo peptide receptor targeting, namely to know which peptide receptor is expressed in which type of cancer, is an important prerequisite for successful clinical application of this technology. In this short review, I give three selected examples of new and promising peptide receptor targets. In the somatostatin receptor field, based on in vitro receptor autoradiography experiments showing that much more sst(2) binding sites are detected in tumors using a (177)Lu-labeled sst(2) antagonist than a (177)Lu-labeled agonist, it can be proposed that, in addition to neuroendocrine tumors, nonneuroendocrine tumors with lower sst(2) levels such as breast carcinomas, renal cell carcinomas, and non-Hodgkin lymphomas may become potential candidates for sst(2) antagonist targeting...
2013: Recent Results in Cancer Research
Diana Boj-Carceller
Diabetes mellitus is a complex chronic disease associated with an absolute insulin deficiency in type 1 diabetes (T1D) and a progressive deterioration of β-cell function in type 2 diabetes (T2D). T2D pathophysiology has numerous defects including incretin deficiency/resistance. Gastrin has demonstrated to be an islet growth factor (like glucagon-like peptide-1, epidermal growth factor, transforming growth factor-α,…) and be able to restore a functional β-cell mass in diabetic animals. This hormone is likely to stimulate insulin secretion during an ordinary protein-rich meal, this is, to have an incretin-like effect...
February 2013: Endocrine
J F Rehfeld
Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man...
April 2011: Acta Physiologica
Noriyasu Kamei, Mariko Morishita, Kozo Takayama
Our previous reports showed that the absorption of therapeutic peptides and proteins was significantly improved by coadministration of cell-penetrating peptides (CPPs) as the physical mixture. However, the mechanisms for this improvement are not clear. In the present study, we verified the hypothesis that the electrostatic interaction between drug and CPP is related to the enhancing effect of the CPP on the intestinal absorption of therapeutic peptides and proteins. In this study, the intermolecular binding was analyzed by surface plasmon resonance (SPR)-based binding assay, and the effect of CPPs on the intestinal absorption of peptide drugs was examined by in situ absorption study using a rat intestinal loop...
June 19, 2009: Journal of Controlled Release: Official Journal of the Controlled Release Society
Carolyn F Deacon
The incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine cells located in the intestinal mucosa, and act to enhance meal-induced insulin secretion. GIP and GLP-1 concentrations in the plasma rise rapidly after food ingestion, and the presence of unabsorbed nutrients in the intestinal lumen is a strong stimulus for their secretion. Nutrients can stimulate release of both hormones by direct contact with the K-cell (GIP) and L-cell (GLP-1), and this may be the most important signal...
June 15, 2005: Regulatory Peptides
Werner Creutzfeldt
The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results. In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years...
June 15, 2005: Regulatory Peptides
K Filipsson, J J Holst, B Ahrén
Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to pancreatic ganglia governing the parasympathetic nerves, which contribute to prandial insulin secretion. We hypothesized that this contribution involves PACAP and show here that the PACAP receptor antagonist PACAP-(6---27) (1.5 nmol/kg iv) reduces the 15-min insulin response to gastric glucose (150 mg/mouse) by 18% in anesthetized mice (P = 0.041). The reduced insulinemia was not due to inhibited release of the incretin factor glucagon-like peptide 1 (GLP-1) because PACAP-(6---27) enhanced the GLP-1 response to gastric glucose...
August 2000: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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