Talk:Endocrine - Pancreas Development
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Cite this page: Hill, M.A. (2024, April 18) Embryology Endocrine - Pancreas Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Endocrine_-_Pancreas_Development |
10 Most Recent Papers
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Pancreas Embryology
<pubmed limit=5>Pancreas Embryology</pubmed>
Pancreas Development
<pubmed limit=5>Pancreas Development</pubmed>
2013
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2012
Metabolic manifestations of insulin deficiency do not occur without glucagon action
Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14972-6. Epub 2012 Aug 13.
Lee Y, Berglund ED, Wang MY, Fu X, Yu X, Charron MJ, Burgess SC, Unger RH. Source Touchstone Center for Diabetes Research, Hypothalamic Research Center, Department of Internal Medicine, and Advanced Imaging Research Center, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Abstract
To determine unambiguously if suppression of glucagon action will eliminate manifestations of diabetes, we expressed glucagon receptors in livers of glucagon receptor-null (GcgR(-/-)) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) mice developed fatal diabetic ketoacidosis after streptozotocin, whereas GcgR(-/-) mice with similar β-cell destruction remained clinically normal without hyperglycemia, impaired glucose tolerance, or hepatic glycogen depletion. Restoration of receptor expression using adenovirus containing the GcgR cDNA restored hepatic GcgR, phospho-cAMP response element binding protein (P-CREB), and phosphoenol pyruvate carboxykinase, markers of glucagon action, rose dramatically and severe hyperglycemia appeared. When GcgR mRNA spontaneously disappeared 7 d later, P-CREB declined and hyperglycemia disappeared. In conclusion, the metabolic manifestations of diabetes cannot occur without glucagon action and, once present, disappear promptly when glucagon action is abolished. Glucagon suppression should be a major therapeutic goal in diabetes.
PMID 22891336
2011
Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
Proc Natl Acad Sci U S A. 2011 Nov 14. [Epub ahead of print]
Rovira M, Huang W, Yusuff S, Shim JS, Ferrante AA, Liu JO, Parsons MJ. Source Departments of Surgery, Pharmacology and Molecular Sciences, and Department of Oncology, and McKusick-Nathans Institute for Genetic Medicine, The Johns Hopkins University, Baltimore, MD 21205.
Abstract
Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.
PMID 22084084
http://www.pnas.org/content/108/48/19264.abstract?etoc Proc Natl Acad Sci U S A.
Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development
PLoS One. 2011;6(11):e27879. Epub 2011 Nov 17.
Xia F, Dohi T, Martin NM, Raskett CM, Liu Q, Altieri DC. Source Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Abstract
The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT) Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin(+) β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA) silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo.
PMID 22114719
Early-life origins of type 2 diabetes: fetal programming of the Beta-cell mass
Exp Diabetes Res. 2011;2011:105076. Epub 2011 Oct 24.
Portha B, Chavey A, Movassat J. Source Université Paris-Diderot, Sorbonne-Paris-Cité, Laboratoire B2PE (Biologie et Pathologie du Pancréas Endocrine), Unité BFA (Biologie Fonctionnelle et Adaptive), EAC 4413 Centre National de la Recherche Scientifique, 75205 Paris, France.
Abstract
A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission.
PMID 22110471
Pancreatic mesenchyme regulates epithelial organogenesis throughout development
PLoS Biol. 2011 Sep;9(9):e1001143. Epub 2011 Sep 6.
Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC, Hebrok M. Source Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
Abstract
The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT) at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR) in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an essential mediator of this process. These results have implications for developing strategies to expand pancreas progenitors and β-cells for clinical transplantation.
PMID 21909240
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001143
2010
Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos
Liang J, Gui Y, Wang W, Gao S, Li J, Song H. Birth Defects Res A Clin Mol Teratol. 2010 Jun;88(6):480-6.
BACKGROUND: Maternal diabetes increases the risk of congenital heart defects in infants, and hyperglycemia acts as a major teratogen. Multiple steps of cardiac development, including endocardial cushion morphogenesis and development of neural crest cells, are challenged under elevated glucose conditions. However, the direct effect of hyperglycemia on embryo heart organogenesis remains to be investigated.
METHODS: Zebrafish embryos in different stages were exposed to D-glucose for 12 or 24 hr to determine the sensitive window during early heart development. In the subsequent study, 6 hr post-fertilization embryos were treated with either 25 mmol/liter D-glucose or L-glucose for 24 hr. The expression of genes was analyzed by whole-mount in situ hybridization.
RESULTS: The highest incidence of cardiac malformations was found during 6-30 hpf exposure periods. After 24 hr exposure, D-glucose-treated embryos exhibited significant developmental delay and diverse cardiac malformations, but embryos exposed to L-glucose showed no apparent phenotype. Further investigation of the origin of heart defects showed that cardiac looping was affected earliest, while the specification of cardiac progenitors and heart tube assembly were complete. Moreover, the expression patterns of tbx5, tbx20, and has2 were altered in the defective hearts.
CONCLUSIONS: Our data demonstrate that elevated glucose alone induces cardiac defects in zebrafish embryos by altering the expression pattern of tbx5, tbx20, and has2 in the heart. We also show the first evidence that cardiac looping is affected earliest during heart organogenesis. These research results are important for devising preventive and therapeutic strategies aimed at reducing the occurrence of congenital heart defects in diabetic pregnancy.
PMID: 20306498 http://www.ncbi.nlm.nih.gov/pubmed/20306498
Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries
Jin ZW, Yu HC, Cho BH, Kim HT, Kimura W, Fujimiya M, Murakami G. Yonsei Med J. 2010 May;51(3):398-406.
PURPOSE: The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head. MATERIALS AND METHODS: In human fetuses between 8-30 weeks, we described the topographical anatomy of the vessels, bile duct, duodenum as well as the ventral and dorsal primordia of the pancreatic head with an aid of pancreatic polypeptide immunohisto-chemistry. RESULTS: The contents of the hepatoduodenal ligament crossed the superior side of the pylorus. Moreover, the right hepatic artery originating from the superior mesenteric artery ran along the superior aspect of the pancreatic head. An arterial arcade, corresponding to the posterior pancreaticoduodenal arteries, encircled the superior part of the pancreatic head, whereas another arcade, corresponding to the anterior pancreaticoduodenal arteries, surrounded the inferior part. The dorsal promordium of the pancreas surrounded and/or mixed the ventral primordium at 13-16 weeks. Thus, both arterial arcades were likely to attach to the dorsal primordium. CONCLUSION: The fetal anatomy of the pancreaticoduodenal vascular arcades as well as that of the hepatoduodenal ligament were quite different from adults in topographical relations. Thus, in the stage later than 30 weeks, further rotation of the duodenum along a horizontal axis seemed to be required to move the pylorus posterosuperiorly and to reflect the superior surface of the pancreatic head posteriorly. However, to change the topographical anatomy of the superior and inferior arterial arcades into the final position, re-arrangement of the pancreatic parenchyma might be necessary in the head.
PMID: 20376893 http://www.ncbi.nlm.nih.gov/pubmed/20376893
http://www.eymj.org/search.php?where=aview&id=128080&code=0069YMJ&vmode=AFTR
Wolcott-Rallison syndrome
Orphanet J Rare Dis. 2010 Nov 4;5:29.
Julier C, Nicolino M.
Inserm UMR-S 958, Faculté de Médecine Denis-Diderot, Paris, France. cecile.julier@inserm.fr
Abstract Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disease, characterized by neonatal/early-onset non-autoimmune insulin-requiring diabetes associated with skeletal dysplasia and growth retardation. Fewer than 60 cases have been described in the literature, although WRS is now recognised as the most frequent cause of neonatal/early-onset diabetes in patients with consanguineous parents. Typically, diabetes occurs before six months of age, and skeletal dysplasia is diagnosed within the first year or two of life. Other manifestations vary between patients in their nature and severity and include frequent episodes of acute liver failure, renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Bone fractures may be frequent. WRS is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3), also known as PKR-like endoplasmic reticulum kinase (PERK). PERK is an endoplasmic reticulum (ER) transmembrane protein, which plays a key role in translation control during the unfolded protein response. ER dysfunction is central to the disease processes. The disease variability appears to be independent of the nature of the EIF2AK3 mutations, with the possible exception of an older age at onset; other factors may include other genes, exposure to environmental factors and disease management. WRS should be suspected in any infant who presents with permanent neonatal diabetes associated with skeletal dysplasia and/or episodes of acute liver failure. Molecular genetic testing confirms the diagnosis. Early diagnosis is recommended, in order to ensure rapid intervention for episodes of hepatic failure, which is the most life threatening complication. WRS should be differentiated from other forms of neonatal/early-onset insulin-dependent diabetes based on clinical presentation and genetic testing. Genetic counselling and antenatal diagnosis is recommended for parents of a WRS patient with confirmed EIF2AK3 mutation. Close therapeutic monitoring of diabetes and treatment with an insulin pump are recommended because of the risk of acute episodes of hypoglycaemia and ketoacidosis. Interventions under general anaesthesia increase the risk of acute aggravation, because of the toxicity of anaesthetics, and should be avoided. Prognosis is poor and most patients die at a young age. Intervention strategies targeting ER dysfunction provide hope for future therapy and prevention.
PMID: 21050479
2009
Remodelling sympathetic innervation in rat pancreatic islets ontogeny
Cabrera-Vásquez S, Navarro-Tableros V, Sánchez-Soto C, Gutiérrez-Ospina G, Hiriart M. BMC Dev Biol. 2009 Jun 17;9:34. PMID: 19534767
http://www.ncbi.nlm.nih.gov/pubmed/19534767
- "Adult pancreatic β cells secrete insulin in response to an increase in extracellular glucose. At birth, this response is not fully developed as neonate β-cells are insensitive to glucose and synthesize and secrete less insulin than adults [1]. Pancreatic islets are innervated by autonomic fibres. In particular, sympathetic neural cell bodies are located in the superior mesenteric and celiac ganglia and are components of the splanchnic nerve and parasympathetic innervation comes from the vagus nerve [2]."
Conclusion The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life.
1. Navarro-Tableros V, Fiordelisio T, Hernandez-Cruz A, Hiriart M: Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat beta-cells.
Am J Physiol Endocrinol Metab 2007, 292(4):E1018-1029.
2. Salvioli B, Bovara M, Barbara G, De Ponti F, Stanghellini V, Tonini M, Guerrini S, Cremon C, Degli Esposti M, Koumandou M, et al.: Neurology and neuropathology of the pancreatic innervation. Jop 2002, 3(2):26-33
Islet architecture: A comparative study
Islets. 2009 Sep-Oct;1(2):129-36.
Kim A, Miller K, Jo J, Kilimnik G, Wojcik P, Hara M. Source Department of Medicine, The University of Chicago, Chicago, IL, USA.
Abstract
Emerging reports on the organization of the different hormone-secreting cell types (alpha, glucagon; beta, insulin; and delta, somatostatin) in human islets have emphasized the distinct differences between human and mouse islets, raising questions about the relevance of studies of mouse islets to human islet physiology. Here, we examine the differences and similarities between the architecture of human and mouse islets. We studied islets from various mouse models including ob/ob and db/db and pregnant mice. We also examined the islets of monkeys, pigs, rabbits and birds for further comparisons. Despite differences in overall body and pancreas size as well as total beta-cell mass among these species, the distribution of their islet sizes closely overlaps, except in the bird pancreas in which the delta-cell population predominates (both in singlets and clusters) along with a small number of islets. Markedly large islets (>10,000 mum(2)) were observed in human and monkey islets as well as in islets from ob/ob and pregnant mice. The fraction of alpha-, beta- and delta-cells within an islet varied between islets in all the species examined. Furthermore, there was variability in the distribution of alpha- and delta-cells within the same species. In summary, human and mouse islets share common architectural features that may reflect demand for insulin. Comparative studies of islet architecture may lead to a better understanding of islet development and function.
PMID: 20606719
Islet size and β-cell ratio for different species
The following species comparison table has been slightly modified from Table 1 data in a recent paper by Kim etal., 2009.[1] Islet size is described as an effective diameter of a circle, which depicts the same area as a measured islet area. β-cell ratio is the area ratio of β-cells in an islet. Both data sets are expressed as the mean value with its standard deviation.
| Species | Age | Islet size (μm) | β-cell ratio |
| Human | 39 years (adult) | 50 ± 29 | 0.64 ± 0.21 |
| Monkey | 1 year | 67 ± 38* | 0.79 ± 0.14* |
| Pig | 6 month | 49 ± 15a | 0.89 ± 0.11* |
| Rabbit | 6 month | 64 ± 28* | 0.79 ± 0.17* |
| Bird | 40 day | 24 ± 6* | 0.46 ± 0.24* |
| Wild-type mouse | 6 month | 116 ± 80* | 0.85 ± 0.14* |
| Pregnant mouse | 3 month | 112 ± 94* | 0.84 ± 0.22* |
| ob/ob mouse | 15 week | 86 ± 76* | 0.92 ± 0.11* |
| db/db mouse | 15 week | 47 ± 24b | 0.53 ± 0.24c |
*p < 0.0001 compared with human.
ap = 0.65
bp = 0.42
cp = 0.0004
Reference
- ↑ <pubmed>20606719</pubmed>
2005
Wnt5 signaling in vertebrate pancreas development
BMC Biol. 2005 Oct 24;3:23.
Kim HJ, Schleiffarth JR, Jessurun J, Sumanas S, Petryk A, Lin S, Ekker SC. Source Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA. kimx0183@umn.edu Abstract BACKGROUND: Signaling by the Wnt family of secreted glycoproteins through their receptors, the frizzled (Fz) family of seven-pass transmembrane proteins, is critical for numerous cell fate and tissue polarity decisions during development.
RESULTS: We report a novel role of Wnt signaling in organogenesis using the formation of the islet during pancreatic development as a model tissue. We used the advantages of the zebrafish to visualize and document this process in living embryos and demonstrated that insulin-positive cells actively migrate to form an islet. We used morpholinos (MOs), sequence-specific translational inhibitors, and time-lapse imaging analysis to show that the Wnt-5 ligand and the Fz-2 receptor are required for proper insulin-cell migration in zebrafish. Histological analyses of islets in Wnt5a(-/-) mouse embryos showed that Wnt5a signaling is also critical for murine pancreatic insulin-cell migration.
CONCLUSION: Our results implicate a conserved role of a Wnt5/Fz2 signaling pathway in islet formation during pancreatic development. This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease.
PMID 16246260
