Endocrine - Pancreas Development
|Embryology - 2 May 2016 Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Pancreas Development
- 4 Human Pancreas Timeline
- 5 Fetal Pancreas
- 6 Developing Pancreatic Islets
- 7 Adult Pancreatic Islets
- 8 Islet size for Different Species
- 9 Hormones
- 10 Molecular
- 11 Pancreas Histology
- 12 Diabetes
- 13 Abnormalities
- 14 References
- 15 Additional Images
- 16 External Links
- 17 Glossary Links
The pancreas is a two-headed organ, not only in origin but also in function. In origin, the pancreas develops from two separate primordia. In function, the organ has both endocrine function in relation to regulating blood glucose (and also other hormone secretions) and gastrointestinal function as an exocrine (digestive) organ, see Gastrointestinal Tract - Pancreas Development.
In recent years there has been much research due to the increasing incidence of diabetes in humans and the potential for stem cell therapeutics. Much is now known about the epithelial/mesenchymal and molecular regulation of pancres development.
At the foregut/midgut junction the septum transversum generates 2 pancreatic buds (dorsal and ventral endoderm) which will fuse to form the pancreas. The dorsal bud arises first and generates most of the pancreas. The ventral bud arises beside the bile duct and forms only part of the head and uncinate process of the pancreas.
In the fetal period islet cell clusters (icc) differentiate from pancratic bud endoderm. These cell clusters form acini and ducts (exocrine). On the edge of these cell clusters pancreatic islets (endocrine) also form. Pancreatic hormonal function is to secrete insulin and glucagon which together regulate blood glucose levels and also somaostatin.
The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth.
- Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume
- Exocrine function - begins after birth
- Endocrine function - from 10 to 15 weeks onward hormone release
- exact roles of hormones in regulating fetal growth?
- Endocrine Links: Introduction | BGD Lecture | Science Lecture | Pineal | Hypothalamus | Pituitary | Thyroid | Parathyroid | Thymus | Pancreas | Adrenal | Gonad | Placenta | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine | Lecture - Gastrointestinal Development | Abnormal Development - Maternal Diabetes | Gastrointestinal Tract - Pancreas Development
Some Recent Findings
|More recent papers|
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Senay Topsakal, Ozlem Ozmen, Fatma Nihan Cankara, Sukriye Yesilot, Dilek Bayram, Nilüfer Genç Özdamar, Sümeyra Kayan Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity. Pancreatology: 2016; PubMed 27025195
Saki Ueno, Shigehito Yamada, Chigako Uwabe, Jörg Männer, Naoto Shiraki, Tetsuya Takakuwa The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13. Anat Rec (Hoboken): 2016, 299(4);439-449 PubMed 26995337
S Aydin, T Kuloglu, M R Ozercan, S Albayrak, S Aydin, U Bakal, M Yilmaz, M Kalayci, M Yardim, M Sarac, A Kazez, H Kocdor, B Kanat, Ih Ozercan, M Gonen, M Bilgen, F Balgetir Irisin immunohistochemistry in gastrointestinal system cancers. Biotech Histochem: 2016;1-9 PubMed 26963139
Ahmed M Abdellatif, Hisashi Oishi, Takahiro Itagaki, Yunshin Jung, Hossam H Shawki, Yukari Okita, Yoshikazu Hasegawa, Hiroyuki Suzuki, Salah E El-Morsy, Mesbah A El-Sayed, Mahmoud B Shoaib, Fumihiro Sugiyama, Satoru Takahashi β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development. PLoS ONE: 2016, 11(2);e0150010 PubMed 26901059
Changzheng Mu, Tao Wang, Xiaomei Wang, He Tian, Yong Liu Identification of microRNAs regulating Hlxb9 gene expression during the induction of insulin-producing cells. Cell Biol. Int.: 2016; PubMed 26801823
- Pancreatic buds - duodenal level endoderm, splanchnic mesoderm forms dorsal and ventral mesentery, dorsal bud (larger, first), ventral bud (smaller, later)
- Pancreas Endoderm - pancreas may be opposite of liver
- Heart cells promote/notochord prevents liver formation
- Notochord may promote pancreas formation
- Heart may block pancreas formation
- Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds
- Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function
- Islet cells - cords of endodermal cells form ducts, from which cells bud off to form islets
Human Pancreas Timeline
- Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin
- Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins
- Week 15 - glucagon detectable in fetal plasma
Mouse pancreas duct development cartoon
Pig embryo (14 mm CRL) (ventral and dorsal)
Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries.
A diagram showing joining processes between the dorsal and ventral primordia of the pancreas as well as the hypothetical rotation of the duodenum along a left-right axis. Viewed from the posterosuperior side of the body. A horizontal plane including most parts of the duodenum is shown to emphasize, in contrast to adults, the course of the second portion (D2) directing posteriorly rather than inferiorly.
Developing Pancreatic Islets
|Model of endocrine cell and vessel organization in human islets||A α-Cells (green) and β-cells (red) are organized into a thick folded plate lined at both sides with vessels (blue).
Adult Pancreatic Islets
The adult pancreatic islets (Islets of Langerhans) contain four distinct endocrine cell types.
- glucagon, mobilizes lipid
- insulin, increase glucose uptake
- stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant
Molecular - Nkx6.1 - NK2 Homeobox 6.1
- homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain.
- required for beta cells development and is completely conserved between rat, mouse, and human.
- somatostatin, inhibits glucagon, insulin secretion
- pancreatic polypeptide
Rat - pancreatic islet development
Islet size for Different Species
The following species comparison table has been slightly modified from Table 1 data in a recent paper by Kim etal., 2009.
- 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 ap = 0.65 bp = 0.42 cp = 0.0004 compared with human.
- Source - synthesized by the beta cells of the islets of Langerhans.
- 2 dissimilar polypeptide chains, A and B, which are linked by 2 disulphide bonds.
- both chains are derived from a 1-chain precursor, proinsulin.
- proinsulin - converted to insulin by the enzymatic removal of a segment that connects the amino end of the A chain to the carboxyl end of the B chain.
- Links: OMIM
- Source - synthesized by the alpha cells of the islets of Langerhans.
- 29-amino acid hormone
- human, rabbit, rat, pig, and cow proteins are identical.
- member of a multigene family that includes - secretin, vasoactive intestinal peptide, gastric inhibitory peptide, glicentin, and others.
- counteracts the glucose-lowering action of insulin
- stimulates glycogenolysis and gluconeogenesis.
- Links: OMIM
Molecular Development of Endocrine Pancreas Cells
- Links: Molecular Development
- Pancreas Histology Links: overview (label) | exocrine (label) | endocrine (label) | blood vessels (label) | insulin (label) | overview | exocrine | endocrine | blood vessels | insulin | Islet labeled for insulin and Glucagon | Insulin (Fl) | Glucagon (Fl) | GIT Histology
- Links: Maternal Diabetes
Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development".
Accessory Pancreatic Tissue - pancreatic tissue located in associated gastrointestinal tract tissues/organs such as the wall of the stomach, duodenum, jejunum or Meckel's diverticulum.
Annular Pancreas - (1 in 7,000 people) pancreas forms as a "ring" of tissue surrounding the duodenum which is subsequently narrowed.
Diabetes Mellitus - Maternal diabetes (and hyperglycaemia) have been shown to lead to increased fetal islet hyperplasia of the insulin producing beta cells and insulin secretion.
Intrauterine growth restriction - can lead to a delayed development of the insulin producing beta cells and low insulin secretion.
Tumours - Serous Cystadenoma (endocrine tumour), Somatostatinoma (tumour of delta cell origin), intraductal papillary-mucinous neoplasm
- Raphaël Scharfmann, Xiangwei Xiao, Harry Heimberg, Jacques Mallet, Philippe Ravassard Beta cells within single human islets originate from multiple progenitors. PLoS ONE: 2008, 3(10);e3559 PubMed 18958289 | PLoS ONE
- Yaron Suissa, Judith Magenheim, Miri Stolovich-Rain, Ayat Hija, Patrick Collombat, Ahmed Mansouri, Lori Sussel, Beatriz Sosa-Pineda, Kyle McCracken, James M Wells, R Scott Heller, Yuval Dor, Benjamin Glaser Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas. PLoS ONE: 2013, 8(8);e70397 PubMed 23940571 | PLoS One.
- Meritxell Rovira, Wei Huang, Shamila Yusuff, Joong Sup Shim, Anthony A Ferrante, Jun O Liu, Michael J Parsons Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation. Proc. Natl. Acad. Sci. U.S.A.: 2011, 108(48);19264-9 PubMed 22084084 | Proc Natl Acad Sci U S A.
- Limor Landsman, Amar Nijagal, Theresa J Whitchurch, Renee L Vanderlaan, Warren E Zimmer, Tippi C Mackenzie, Matthias Hebrok Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol.: 2011, 9(9);e1001143 PubMed 21909240 | PLoS Biol.
- Petra Dames, Ramona Puff, Michaela Weise, Klaus G Parhofer, Burkhard Göke, Magdalena Götz, Jochen Graw, Jack Favor, Andreas Lechner Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev. Biol.: 2010, 10;39 PubMed 20377917
- Zhe Wu Jin, Hee Chul Yu, Baik Hwan Cho, Hyoung Tae Kim, Wataru Kimura, Mineko Fujimiya, Gen Murakami Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries. Yonsei Med. J.: 2010, 51(3);398-406 PubMed 20376893 | Yonsei Med J.
- Domenico Bosco, Mathieu Armanet, Philippe Morel, Nadja Niclauss, Antonino Sgroi, Yannick D Muller, Laurianne Giovannoni, Géraldine Parnaud, Thierry Berney Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes: 2010, 59(5);1202-10 PubMed 20185817 | PMC2857900 | Diabetes.
- Siraam Cabrera-Vásquez, Víctor Navarro-Tableros, Carmen Sánchez-Soto, Gabriel Gutiérrez-Ospina, Marcia Hiriart Remodelling sympathetic innervation in rat pancreatic islets ontogeny. BMC Dev. Biol.: 2009, 9;34 PubMed 19534767
- Abraham Kim, Kevin Miller, Junghyo Jo, German Kilimnik, Pawel Wojcik, Manami Hara Islet architecture: A comparative study. Islets: 2010, 1(2);129-36 PubMed 20606719
- K Holemans, L Aerts, F A Van Assche Lifetime consequences of abnormal fetal pancreatic development. J. Physiol. (Lond.): 2003, 547(Pt 1);11-20 PubMed 12562919
- Pancreas The official journal of the American Pancreatic Association and the Japan Pancreas Society | PubMed
- Pancreatology Official Journal of the International Association of Pancreatology (IAP); European Pancreatic Club (EPC)and 16 other societies and study groups.
- Journal of the Pancreas electronic journal of pancreatology
- Diabetologia | PubMed
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents
NIH Genes & Disease Chapter 41 - Endocrine
Pathophysiology of the Endocrine System The Endocrine Pancreas
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.
Search Bookshelf Pancreas Development
Amaresh K Ranjan, Mugdha V Joglekar, Anandwardhan A Hardikar Endothelial cells in pancreatic islet development and function. Islets: 2010, 1(1);2-9 PubMed 21084843
Mary D Kinkel, Victoria E Prince On the diabetic menu: zebrafish as a model for pancreas development and function. Bioessays: 2009, 31(2);139-52 PubMed 19204986
George K Gittes Developmental biology of the pancreas: a comprehensive review. Dev. Biol.: 2009, 326(1);4-35 PubMed 19013144
Claire Bonal, Pedro L Herrera Genes controlling pancreas ontogeny. Int. J. Dev. Biol.: 2008, 52(7);823-35 PubMed 18956314
Jennifer M Oliver-Krasinski, Doris A Stoffers On the origin of the beta cell. Genes Dev.: 2008, 22(15);1998-2021 PubMed 18676806
Bernard Portha, Audrey Chavey, Jamileh Movassat Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. Exp Diabetes Res: 2011, 2011;105076 PubMed 22110471
M J Riedel, A Asadi, R Wang, Z Ao, G L Warnock, T J Kieffer Immunohistochemical characterisation of cells co-producing insulin and glucagon in the developing human pancreas. Diabetologia: 2012, 55(2);372-81 PubMed 22038519
Fengxia Ma, Cécile Haumaitre, Fang Chen, Zhongchao Han Comparison of murine embryonic pancreatic development in vitro and in vivo. Pancreas: 2011, 40(7);1012-7 PubMed 21926540
Erin McDonald, Jinming Li, Mansa Krishnamurthy, George F Fellows, Cynthia G Goodyer, Rennian Wang SOX9 regulates endocrine cell differentiation during human fetal pancreas development. Int. J. Biochem. Cell Biol.: 2012, 44(1);72-83 PubMed 21983268
Kai-Ming Yang, Wang Yong, Ai-Dong Li, Hui-Jun Yang Insulin-producing cells are bi-potential and differentiatorsprior to proliferation in early human development. World J Diabetes: 2011, 2(4);54-8 PubMed 21537461
Juris J Meier, Christina U Köhler, Bacel Alkhatib, Consolato Sergi, Theresa Junker, Harald H Klein, Wolfgang E Schmidt, Helga Fritsch Beta-cell development and turnover during prenatal life in humans. Eur. J. Endocrinol.: 2010, 162(3);559-68 PubMed 20022941
Jongmin Jeon, Mayrin Correa-Medina, Camillo Ricordi, Helena Edlund, Juan A Diez Endocrine cell clustering during human pancreas development. J. Histochem. Cytochem.: 2009, 57(9);811-24 PubMed 19365093
Jennifer M Oliver-Krasinski, Margaret T Kasner, Juxiang Yang, Michael F Crutchlow, Anil K Rustgi, Klaus H Kaestner, Doris A Stoffers The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice. J. Clin. Invest.: 2009, 119(7);1888-98 PubMed 19487809
D Eberhard, D Tosh, J M W Slack Origin of pancreatic endocrine cells from biliary duct epithelium. Cell. Mol. Life Sci.: 2008, 65(21);3467-80 PubMed 18810318
Raphaël Scharfmann, Xiangwei Xiao, Harry Heimberg, Jacques Mallet, Philippe Ravassard Beta cells within single human islets originate from multiple progenitors. PLoS ONE: 2008, 3(10);e3559 PubMed 18958289
K Piper, S Brickwood, L W Turnpenny, I T Cameron, S G Ball, D I Wilson, N A Hanley Beta cell differentiation during early human pancreas development. J. Endocrinol.: 2004, 181(1);11-23 PubMed 15072563
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- Endocrine Development - All (14277) Review (4620) Free Full Text (3140)
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External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.
- F1000 Reports - Recent advances in pancreas development
- Howard Hughes Medical Institute - Seung Kim Lab
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Cite this page: Hill, M.A. (2016) Embryology Endocrine - Pancreas Development. Retrieved May 2, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Pancreas_Development
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