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Exocrine pancreas

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https://www.readbyqxmd.com/read/28090569/mitogen-activated-protein-kinase-kinase-activity-maintains-acinar-to-ductal-metaplasia-and-is-required-for-organ-regeneration-in-pancreatitis
#1
Christopher J Halbrook, Hui-Ju Wen, Jeanine M Ruggeri, Kenneth K Takeuchi, Yaqing Zhang, Marina Pasca di Magliano, Howard C Crawford
BACKGROUND & AIMS: Mitogen-activated protein kinase (MAPK) signaling in the exocrine pancreas has been extensively studied in the context of pancreatic cancer, where its potential as a therapeutic target is limited by acquired drug resistance. However, its role in pancreatitis is less understood. We investigated the role of mitogen-activated protein kinase kinase (MEK)-initiated MAPK signaling in pancreatitis to determine the potential for MEK inhibition in treating pancreatitis patients...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28089869/the-molecular-and-morphogenetic-basis-of-pancreas-organogenesis
#2
REVIEW
Hjalte List Larsen, Anne Grapin-Botton
The pancreas is an essential endoderm-derived organ that ensures nutrient metabolism via its endocrine and exocrine functions. Here we review the essential processes governing the embryonic and early postnatal development of the pancreas discussing both the mechanisms and molecules controlling progenitor specification, expansion and differentiation. We elaborate on how these processes are orchestrated in space and coordinated with morphogenesis. We draw mainly from experiments conducted in the mouse model but also from investigations in other model organisms, complementing a recent comprehensive review of human pancreas development (Jennings et al...
January 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#3
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
December 27, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28087712/pdx1-dynamically-regulates-pancreatic-ductal-adenocarcinoma-initiation-and-maintenance
#4
Nilotpal Roy, Kenneth K Takeuchi, Jeanine M Ruggeri, Peter Bailey, David Chang, Joey Li, Laura Leonhardt, Sapna Puri, Megan T Hoffman, Shan Gao, Christopher J Halbrook, Yan Song, Mats Ljungman, Shivani Malik, Christopher V E Wright, David W Dawson, Andrew V Biankin, Matthias Hebrok, Howard C Crawford
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28067253/whole-organ-and-islet-of-langerhans-dosimetry-for-calculation-of-absorbed-doses-resulting-from-imaging-with-radiolabeled-exendin
#5
Inge van der Kroon, Wietske Woliner-van der Weg, Maarten Brom, Lieke Joosten, Cathelijne Frielink, Mark W Konijnenberg, Eric P Visser, Martin Gotthardt
Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057752/foxo1-inhibits-accelerated-%C3%AE-cell-aging-in-pancreas-specific-smad7-mutant-mice
#6
Xiangwei Xiao, Congde Chen, Ping Guo, Ting Zhang, Shane Fischbach, Joseph Carl Fusco, Chiyo Shiota, Krishna Prasadan, H Henry Dong, George K Gittes
The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here, we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β-cell dysfunction, with accelerated glucose intolerance, followed by overt diabetes. The accelerated β-cell dysfunction and loss of proliferation capacity, two features of β-cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a bystander effect. Increased FoxO1 acetylation and nuclear retention was followed by progressive FoxO1 loss in β-cells, which marked the onset of diabetes...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28055028/the-role-of-gut-brain-axis-in-regulating-glucose-metabolism-after-acute-pancreatitis
#7
Sayali A Pendharkar, Varsha M Asrani, Rinki Murphy, Richard Cutfield, John A Windsor, Maxim S Petrov
OBJECTIVES: Diabetes has become an epidemic in developed and developing countries alike, with an increased demand for new efficacious treatments. A large body of pre-clinical evidence suggests that the gut-brain axis may be exploited as a potential therapeutic target for defective glucose homeostasis. This clinical study aimed to investigate a comprehensive panel of glucoregulatory peptides, released by both the gut and brain, in individuals after acute pancreatitis. METHODS: Fasting levels of glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, peptide YY, ghrelin, cholecystokinin, vasoactive intestinal peptide (VIP), and secretin were studied...
January 5, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28050357/evaluation-of-biochemical-markers-serum-amylase-and-serum-lipase-for-the-assessment-of-pancreatic-exocrine-function-in-diabetes-mellitus
#8
Mahesh Basavaraj Madole, Chandrashekhar M Iyer, Mamatha Thimmanna Madivalar, Satish Kishanrao Wadde, Deepak Sadashiv Howale
INTRODUCTION: Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycaemia, associated with deficiency or resistance to insulin indicates endocrinal abnormality of the pancreas. Amylase and lipase are enzymes secreted by the exocrine portion of the pancreas. Endocrinal derangement observed in diabetes may interfere with the exocrine function of the pancreas. AIM: To estimate the levels of fasting blood sugar, serum lipase, serum amylase in patients of type 1 and type 2 DM...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28050352/morphometric-study-of-pancreas-in-human-fetuses
#9
Abhijeet S Dhende, Mahendra A Kathole, Deepak S Joshi
INTRODUCTION: The pancreas arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. It extends transversely across the posterior abdominal wall from the duodenum to the spleen. Functionally, it is endocrine and exocrine. AIM: This study was undertaken to study the morphometry of human pancreas at different gestational age groups of normal, still born fetuses. MATERIALS AND METHODS: Forty aborted human fetuses (25 male and 15 female) of 12-40 weeks gestational age with no obvious congenital abnormality were obtained...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28050116/lipomatous-pseudohypertrophy-of-pancreas-with-coexisting-chronic-calcific-pancreatitis-leading-to-malabsorption-due-to-exocrine-pancreatic-insufficiency
#10
Devendra Nema, Sumeet Arora, Ashutosh Mishra
No abstract text is available yet for this article.
December 2016: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28049534/case-report-maternal-mosaicism-resulting-in-inheritance-of-a-novel-gata6-mutation-causing-pancreatic-agenesis-and-neonatal-diabetes-mellitus
#11
Daphne Yau, Elisa De Franco, Sarah E Flanagan, Sian Ellard, Miriam Blumenkrantz, John J Mitchell
BACKGROUND: Haploinsufficiency of the GATA6 transcription factor gene was recently found to be the most common cause of pancreatic agenesis, a rare cause of neonatal diabetes mellitus. Although most cases are de novo, we describe three siblings with inherited GATA6 haploinsufficiency and the rare finding of parental mosaicism. CASE PRESENTATION: The proband was born at term with severe intrauterine growth restriction, the first child of non-consanguineous parents...
January 3, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28027633/pancreatic-exocrine-insufficiency-in-malnourished-children-and-those-with-persistent-diarrhoeae
#12
Ariani Dewi Widodo, Ina S Timan, Saptawati Bardosono, Widdy Winarta, Dwi Prasetyo, Agus Firmansyah
BACKGROUND AND OBJECTIVES: Persistent diarrhoea, a serious health problem, is closely related to malnutrition. Children with severe malnutrition have a 9-fold risk of death, and children with severe stunting have a 4-fold risk of death. Prolonged mucosal injury from diarrhoea causes reduced secretin and cholecystokinin secretion, which decreases stimulation to the pancreas, and is indicated by faecal elastase-1 levels. This further aggravates persistent diarrhoea and malnutrition because of the low levels of digestive enzyme production...
December 2016: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28013573/evaluation-of-mir-216a-and-mir-217-as-potential-biomarkers-of-acute-exocrine-pancreatic-toxicity-in-rats
#13
Jianying Wang, Wenhu Huang, Stephane Thibault, Thomas P Brown, Walter Bobrowski, Hovhannes J Gukasyan, Winston Evering, Wenyue Hu, Annette John-Baptiste, Allison Vitsky
Detecting and monitoring exocrine pancreatic damage during nonclinical and clinical testing is challenging because classical biomarkers amylase and lipase have limited sensitivity and specificity. Novel biomarkers for drug-induced pancreatic injury are needed to improve safety assessment and reduce late-stage attrition rates. In a series of studies, miR-216a and miR-217 were evaluated as potential biomarkers of acute exocrine pancreatic toxicity in rats. Our results revealed that miR-216a and miR-217 were almost exclusively expressed in rat pancreas and that circulating miR-216a and miR-217 were significantly increased in rats following administration of established exocrine pancreatic toxicants caerulein (CL) and 1-cyano-2-hydroxy-3-butene (CHB) as well as in rats administered a proprietary molecule known to primarily affect the exocrine pancreas...
January 1, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/28012279/pancreas-volume-and-fat-deposition-in-diabetes-and-normal-physiology-consideration-of-the-interplay-between-endocrine-and-exocrine-pancreas
#14
Yoshifumi Saisho
The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes...
July 2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/27974199/glucagon-like-peptide-1-receptor-signaling-in-acinar-cells-causes-growth-dependent-release-of-pancreatic-enzymes
#15
Nicolai J Wewer Albrechtsen, Reidar Albrechtsen, Lasse Bremholm, Berit Svendsen, Rune E Kuhre, Steen S Poulsen, Charlotte B Christiansen, Elisa P Jensen, Charlotte Janus, Linda Hilsted, Carolyn F Deacon, Bolette Hartmann, Jens J Holst
Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27941193/comparison-of-72-hour-fecal-fat-quantification-and-the-13c-mixed-triglyceride-breath-test-in-assessing-pancreatic-exocrine-sufficiency-in-children-with-chronic-pancreatitis
#16
Karolina Wejnarska, Elwira Kołodziejczyk, Józef Ryżko, Grzegorz Oracz
INTRODUCTION: Chronic pancreatitis (CP) in children is still a rare, although increasingly recognized entity. Over the duration of the disease several complications can be observed, two of which are major ones: endo- and exocrine insufficiency. In the medical care of children with CP it is crucial to diagnose the decreased endo- and exocrine function of the pancreas, in order to preserve patients from malnutrition and the failure to thrive. The aim of the study was to compare the usefulness of two indirect methods of assessing the pancreas exocrine function in children with CP...
2016: Developmental Period Medicine
https://www.readbyqxmd.com/read/27941156/efficacy-of-pancreatic-enzyme-replacement-therapy-in-chronic-pancreatitis-systematic-review-and-meta-analysis
#17
Daniel de la Iglesia-García, Wei Huang, Peter Szatmary, Iria Baston-Rey, Jaime Gonzalez-Lopez, Guillermo Prada-Ramallal, Rajarshi Mukherjee, Quentin M Nunes, J Enrique Domínguez-Muñoz, Robert Sutton
OBJECTIVE: The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. DESIGN: Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined...
December 9, 2016: Gut
https://www.readbyqxmd.com/read/27933184/coxsackie-adenovirus-receptor-expression-is-enhanced-in-pancreas-from-patients-with-type-1-diabetes
#18
M Hodik, M Anagandula, J Fuxe, L Krogvold, K Dahl-Jørgensen, H Hyöty, L Sarmiento, G Frisk
OBJECTIVES: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. DESIGN: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27903836/sericin-ameliorated-dysmorphic-mitochondria-in-high-cholesterol-diet-streptozotocin-rat-by-antioxidative-property
#19
Sumate Ampawong, Duangnate Isarangkul, Pornanong Aramwit
Sericin has been implicated in lower cholesterolemic effect due to its properties with several mechanisms. Mitochondria are one of the most important targets to be affected in high blood cholesterol and glucose conditions. The protective role of sericin on mitochondria remains doubtful. To examine this role, electron microscopic, histopathologic, immunohistochemical, and biochemical studies were performed in a high-cholesterol diet/streptozotocin rat model. The results demonstrated that sericin reduced blood cholesterol without hypoglycemic effect...
November 29, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27896656/pancreatitis-after-pancreatoduodenectomy-predicts-clinically-relevant-postoperative-pancreatic-fistula
#20
C M Kühlbrey, N Samiei, O Sick, F Makowiec, U T Hopt, U A Wittel
BACKGROUND: Morbidity after pancreas resection is still high with postoperative pancreatic fistulas (POPF) being the most frequent complication. However, exocrine insufficiency seems to protect from POPF. In clinical practice, patients showing increased postoperative systemic amylase concentrations appear to frequently develop POPF. We therefore retrospectively examined the occurrence of systemic amylase increase after pancreas resections and its association with the clinical course. PATIENTS AND METHODS: Perioperative data from 739 consecutive pancreas resections were assessed in a prospectively maintained SPSS database...
November 28, 2016: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
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